Turning 15 and driving continued,
‘crystalized’ progress against cancer
during COVID-19 pandemic waves

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Foreword by VHIO’s Director

2021: Turning 15 and driving continued, ‘crystalized’ progress against cancer during COVID-19 pandemic waves

Josep Tabernero
Director, Vall d'Hebron Institute of Oncology (VHIO)

This year’s Scientific Report celebrates our Institute’s 15th year of advancing cancer science and clinical oncology against this disease that will affect an estimated 1 in 2 people during their lifetime.

The simple branding incorporating crystals is symbolic for three reasons. First, in some cultures, crystals are associated with a 15-year anniversary. Second, as evidenced throughout this report, we continue to achieve greater clarity regarding the many complexities that still remain in more effectively combating cancer. Finally, the spherical crystals, emitting energy from all sides, represents VHIO’s multidisciplinary and translational model – a seamless, unrestricted flow of discovery from the bench to bedside and back.

This approach was pioneered by José Baselga, our Institute’s founder and first director, who very sadly passed away at the age of 61 on 21 March, 2021.

The international scientific cancer community, along with all other stakeholders in oncology, continues to mourn his passing. José was a visionary scientific leader and trailblazer in cancer research and precision oncology who made tremendous contributions to improving outcomes for cancer patients worldwide. By integrating patient care within a multidisciplinary program connecting basic, clinical and translational science, he spearhead efforts to rapidly translate cancer discovery into clinical benefits for patients.

This unique research model emboldened him to create VHIO in 2006. From the outset, he had one guiding principle for our Institute. Namely, to seamlessly bridge preclinical and clinical research in order to foster a continuous virtuous cycle of knowledge from bench to bedside and back. This translational approach continues to be at the very core of VHIO’s philosophy, which I, as VHIO’s Director, passionately pursue alongside our multidisciplinary teams.

José was also an exceptionally generous mentor and a much-loved friend. Please refer to the close of this Foreword, Honoring the life and legacy of the father of precision medicine in oncology

José "Pepe" Baselga, MD, PhD (1959-2021): a visionary leader in translational science and precision oncology, and VHIO’s founder and first director.

On behalf of all of us at VHIO, I dedicate this year’s Scientific Report to the treasured memory of José Baselga.


Another element of this year’s design includes the fold-out section that opens this report. I am pleased to announce that our Institute received Excelencia Severo Ochoa accreditation in 2021, and is now recognized as a Severo Ochoa Center of Excellence (2022-2026). Granted as part of the subprogram of the Spanish Institutional Strengthening of the State Plan for Scientific and Technical Research and Innovation, this accolade recognizes national research centers demonstrating scientific leadership of excellence and impact at a global level.

This distinction not only reflects VHIO’s important contributions to cancer science and precision medicine in oncology, but also confirms our capacity to advance frontier research, generate high-impact results, as well as attract and retain research talent. Set within the Vall d’Hebron Barcelona Hospital Campus, VHIO is the first research center closely linked to one of the Spanish National Healthcare System’s Hospitals to have been endorsed by this prestigious seal of excellence.

For a second consecutive year, due to the safety issues brought about by COVID-19, we had to adjust our approach to this year’s photography. With the exception of some of our larger groups, we have moved mountains to ensure that as many group members as possible have been included, and without masks. Each photograph was shot at a distance, in locations away from areas dedicated to the care of our cancer patients. For faculty working remotely, we invited them to submit their photos from home.

COVID-19: the impact on cancer patients, clinical research and oncology professionals

In our determined efforts to overcome the challenges posed by COVID-19 pandemic waves, VHIO’s researchers and clinical investigators have continued to drive important advances in cancer discovery and improve the treatment and care of cancer patients.

For another year, we succeeded in weathering the COVID-19 storm. VHIO’s multidisciplinary teams speedily adjusted to shifting circumstances and continued to balance physically working in the lab and/or clinical setting with remote working. In some instances, we continued to adapt conventional cancer care, deviate from existing protocols, and administer novel therapies including immunosuppressive treatment regimens.

Additionally, we have fine-tuned technology-based and remote interventions in patient care in order to minimize on-site monitoring visits and in-person consultations. These measures, which were rapidly adopted at the outbreak of the pandemic in 2020, are flanked by the application of telemedicine. This development is one of the few welcome offshoots of the pandemic. Remote patient care has subsequently stepped up in bringing crucial medical expertise to more patients.

Thanks to our discussions with the Spanish Agency of Medicines and Medical Products (AEMPS), the virtual monitoring of patients in clinical trials was first implemented in Spain. AEMPS subsequently supported this move which enabled us to continue conducting essential clinical research.

At VHIO, we firmly believe in turning challenges into opportunities. This ethos drives us to steadfastly pursue our preclinical, translational and clinical research to improve the early detection, diagnosis and treatment of cancer.

As importantly, like many other biomedical research institutes, we also joined the historic, scientific effort in the COVID-19 era by leading essential research into the real-world impact of the virus on our cancer patients, oncology professionals, and clinical studies.

Spurring transformative cancer science and clinical research

I can report another record-breaking year in terms of our contributions to translational cancer science and clinical research. In partnership with many other leading research centers and groups, both nationally and internationally, VHIO teams and talents published 446 scientific articles in leading journals as corresponding, senior or co-authors in 2021. This is a remarkable achievement, particularly considering the turbulent pandemic waves.

I take this opportunity to highlight just a few of our studies that rightly made headlines this year, some of which were paradigm-shifting:

Calling the faithful: the predictability and reproducibility of cancer models
The validation of reliable preclinical cancer models

One concern over the reliability and predictive powers of patient-derived cancer xenograft (PDXs) models is whether the mouse host influences tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling in human cancer. The mouse microenvironment of the transplanted tumor has been suggested to induce selective pressures differing from those in humans, causing PDX tumors to adapt and change in ways that are not observed in patients.

The EurOPDX Consortium* partners, including VHIO as a founding member, collaborated with the US-based PDXNet Consortium to assess whether the PDX engraftment process in mice causes tumors to evolve, especially in ways that could affect their suitability for the testing of promising new cancer therapies.

Led by Enzo Medico, University of Torino, Candiolo Cancer Institute FPO-IRCCS (Turin, Italy), and Jeffrey Chuang, Jackson Laboratory for Genomic Medicine (Farmington, CT, USA), the researchers, including several VHIO investigators** with expertise in developing modelling systems including PDXs and organoids, exhaustively analyzed copy number alterations (CNAs) in 1,451 PDXs and matched patient tumor (PT) samples from more than 500 models.

Led by first author Xing Yi Woo (Jackson Laboratory), the findings of this study (1) showed that the differences between the CNA profiles of PDXs and matched patient tumors are generally marginal, randomly distributed and analogous to differences observed between the two pieces of the same patient tumor. These findings confirm that copy number evolution is not aberrantly driven by the mouse host environment.

By confirming that tumors engrafted and passaged in PDXs maintain a high degree of molecular fidelity to the original patient tumors, this research verifies their suitability for preclinical drug testing, and represents a step forward in further validating the reliability of robust preclinical models in cancer research.

* The EDIReX project has received funding from the European Union’s Horizon 2020 research and innovation programme, grant agreement No. 731105.

** This study counted on the expertise of several VHIO preclinical and translational group leaders including co-author Violeta Serra (PI: Experimental Therapeutics Group), and collaborative authors Joaquin Arribas (PI: Growth Factors Group), Héctor G. Palmer (PI: Stem Cells & Cancer Group), Laura Soucek (PI: Models of Cancer Therapies Group), and Alejandro Piris (Head of VHIO’s Scientific Management Area).

Organoid cancer models: promising accelerators of precision medicine

Jose A. Seoane, Principal Investigator, Cancer Computational Biology Group.

At VHIO, we are dedicated to accelerating robust preclinical data required to reliably guide the clinical development of innovative agents and approaches, as well as evidence reproducibility before moving into the clinic. An area of strength is in cancer modelling, with particular emphasis on the fine tuning of PDXs, avatar and organoid models to identify factors governing tumor progression and response to therapy.

To overcome certain limitations of murine models in faithfully recapitulating later stages of carcinogenesis in humans, research co-authored by VHIO’s Jose A. Seoane reinforces the value of primary human organoids. These models of tumorigenesis mimic oncogenic transformation on a collective tissue scale and accurately replicate the in vivo biology of their original native tissues.

In a study (2) directed by Calvin J. Kuo, Stanford University School of Medicine (CA, USA), the investigators leveraged human gastric organoids to establish the first forward genetics human ARID1A transformation model. Multi-omic analysis revealed both the phenotypic and functional capture of several features of ARID1A-mutated gastric cancer.

This strategy revealed essential oncogenic transformation mechanisms of early ARID1A-deficient gastric cancer. This multi-tool method could be extended and applied to other tumor types to generate clinically relevant data on disease initiation and response to therapy.

Immunotherapy: stepping up across tumor types

Unveiled: a novel mechanism of resistance to T-cell bispecific antibodies & CAR-T targeting HER2 breast cancer

Joaquín Arribas, Principal Investigator, Growth Factors & Cancer Group.

Immunotherapy continues to show exciting promise in more effectively combating several tumor types. Many current strategies focus on ensuring the efficient delivery of active cytotoxic cells directly to tumors. Provided that inhibitory mechanisms are in check, it is thought that once the lymphocytes engage to cancer cells, they will unfailingly destroy them.

The redirection of lymphocytes, via T-cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs), is already approved as an approach to treat some hematologic malignancies. But in solid tumors, these immune-based strategies continue to fail. Research led by VHIO’s Joaquín Arribas, revealed how HER2 breast cancer cells adopt a strategy to resist clearance by these redirected lymphocytes (3).

Findings evidenced that the disruption of interferon-gamma signaling enables cancer cells to escape death by lymphocytes, conferring resistance to immunotherapy and promoting disease progression.

These results could help to potentiate future immune-based strategies and more precisely identify those patients who would be most likely to benefit from them. Moving forward, the investigators hope to launch a clinical trial in 2024-25 to advance CAR-T targeting in breast cancer.

Machine learning for grading neoantigens as potential therapeutic targets

Alena Gros, Principal Investigator, Tumor Immunology & Immunotherapy Group.

Tumor neoepitopes are a class of major histocompatibility complex (MHC)-bounded peptides and represent the antigenic determinants of neoantigens. Recognized by tumor-infiltrating lymphocytes (TILs), they can trigger an immune response to cancer and are thus currently being targeted by adoptive T-cell therapies. Identifying mutant neoepitopes from tumor cells that can be detected by T cells could help to develop more effective tumor-specific, cell-based therapies, as well as advance important insights into antitumor responses.

In a study (4) directed by veteran cancer researcher Steven A. Rosenberg and Paul F. Robbins, co-led by Jared J. Gartner, National Cancer Institute, NIH (Bethesda, MD, USA), the researchers, including VHIO’s Alena Gros, describe a novel machine learning model to assess a large dataset of verified tumor neoantigens, along with a corresponding dataset of matched negative candidates from the same samples.

As a ranking algorithm for class I candidate neoepitopes, this tool was developed using next-generation sequencing (NGS) data and a dataset of 185 identified neoepitopes that are recognized by HLA class I-restricted TILs from patients with metastatic cancer, across several tumor types. The scoring output provided a set of candidate neoantigens that could be used as therapeutic targets and facilitate in vitro and in vivo studies aimed at developing more effective immune-based therapies.

Immune checkpoint inhibitor atezolizumab as a potential game changer in early-stage non-small cell lung cancer

Enriqueta Felip, Principal Investigator, Thoracic Tumors & Head and Neck Cancer Group.

The IMpower010 multicenter, open-label, randomized trial was designed to compare the efficacy and safety of an immune checkpoint inhibitor, atezolizumab, compared with best supportive care as adjuvant therapy in patients with stage IB-stage IIIA non-small cell lung cancer (NSCLC), following resection and adjuvant chemotherapy.

Importantly, this was the first clinical trial to demonstrate that immunotherapy significantly improves disease-free survival compared with best supportive care alone, particularly in tumors expressing PD-L1. Building on these primary results, reported at the American Society of Clinical Oncology’s virtual Annual Meeting (ASCO June 2021), data from the IMpower010 interim disease-free analysis were presented by lead investigator, VHIO’s Enriqueta Felip at the European Society for Medical Oncology’s virtual Congress 2021 (ESMO 2021), 16-21 September.

Results from exploratory analyses of sites of disease relapse and subsequent therapy with atezolizumab compared with best supportive care in patients with stage II and III NSCLC, showed significantly less disease recurrence and improved disease-free survival, particularly in those patients whose tumors expressed PD-L1. Reflective of the relevance of these findings, data from this study (5) published in parallel during the ESMO meeting.

This landmark study points to a potential paradigm shift in the treatment of patients with resected, early-stage NSCLC. Results also shine important light on more effectively combating high-risk cancer in the early-stage setting before it spreads, as well as potentially preventing disease recurrence.

Cemiplimab shows promise as the first immune-based therapy to improve overall survival in patients with recurrent and/or metastatic cervical cancer

Ana Oaknin, Principal Investigator, Gynecological Malignancies Group.

Data from the second interim analysis of the multi-center, international Phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial, first authored on behalf of the Gynecologic Oncology Group (GOG) by Krishnansu S. Tewari, University of California, Irvine (CA, USA), were presented at ESMO 2021.

Co-led on behalf of the European Network of Gynecological Oncology Trial groups (ENGOT) by VHIO’s Ana Oaknin, this study (6) assessed the efficacy of PD-1 inhibitor, cemiplimab, as monotherapy, compared with physician’s choice chemotherapy in improving clinical outcomes, measured by overall survival (OS) as the primary endpoint.

This study not only rings in the largest clinical trial to-date in this patient population, it also marks the advent of cemiplimab as the first immune-based therapy to show an improvement in overall survival in patients whose disease progressed on first line treatment with platinum-based chemotherapy. Strikingly, this improvement was observed in all patients irrespective of tumor histology.

The results show great promise in opening up new treatment avenues for these patients. Crucially, women suffering from cervical cancer are most frequently diagnosed between the ages of 35 and 44 years of age. Efforts will continue to center on more effectively combat this terrible disease by significantly extending the survival of these younger cancer patients.

And, in combination:

KEYNOTE-811: pembrolizumab combination as a potentially transformative treatment for HER2-positive gastric cancer

Josep Tabernero, VHIO’s Director and Head of the Medical Oncology Department, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus.

Previous phase II studies combining PD-1 antibody pembrolizumab with trastuzumab plus chemotherapy have shown increased clinical efficacy and a manageable safety profile in patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma (HER2+ GC).

Building on these encouraging results, the randomized, double-blind, global phase III KEYNOTE-811 trial, led by Yelena Y. Janjigian, Memorial Sloan Kettering Cancer Center - MSKCC (New York, USA), was designed to further assess this novel triplet. The initial findings, which were selected to first outing during ASCO 2021, led to the subsequent U.S. Food and Drug Administration (FDA) accelerated approval of the pembrolizumab combination for the first-line treatment of patients with locally advanced unresectable or metastatic HER2+ GC.

The KEYNOTE-811 investigators have most recently reported results from the interim analysis of the first patients who were randomly assigned to receive pembrolizumab or placebo in combination with trastuzumab and chemotherapy. Not only did the combination of pembrolizumab, trastuzumab plus chemotherapy significantly improve overall response rate, it also markedly reduced tumor size and induced complete responses in some patients. Their findings also support preclinical data suggesting a possible synergy between dual HER2 and PD-1 blockade.

This study (7) is the first to show the efficacy of a PD-1 immune checkpoint inhibitor in this particular patient population. Completion of this trial will confirm whether the data translates in improved progression-free survival as well as overall survival.

And, in combination:

Immunotherapy plus selected targeted therapies in patients with previously treated advanced urothelial cancer: negatives into positives

Joan Carles, Principal Investigator, Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group.

Evaluating the efficacy of an anti-PD-L1 antibody, durvalumab, in combination with therapy targeted to tumor mutations in bladder cancer, the adaptive biomarker-directed platform and multi-arm BISCAY phase Ib study led by Thomas Powles, Cancer Research UK - Barts Cancer Centre, St. Bartholomew’s Hospital (London UK), co-authored by VHIO’s Joan Carles, failed to show increased activity for any of the combinations.

Previous studies had already demonstrated the efficacy of durvalumab in chemotherapy-refractory advanced urothelial cancer (AUC), achieving long-lasting remissions in a subset of these patients. Considering that urothelial cancer is characterized by several recurrent targetable genomic alterations, this ambitious trial combined durvalumab with three matched targeted therapies: FGFR, PARP, and TORC1/2 inhibitors. Of these, only FGFR inhibition had previously been tested with positive outcomes in this tumor type.

Eligible patients were assigned to one of six study arms, including durvalumab as monotherapy, to evaluate whether the addition of any of the three different families of inhibitors improved outcomes. Disappointingly, reported response rates did not meet efficacy criteria for further development, and published findings (8) did not provide data pointing to novel treatment approaches.

That said, the results raise important questions regarding the utility of targeted therapy plus immunotherapy in patients with AUC. First, future studies designed to assess the pairing of matched targeted therapies with immunotherapy, and in larger cohorts, could now be avoided, sparing patients’ exposure to ineffective treatment approaches. Second, in their biomarker analyses, the investigators compared genomic profiling by liquid biopsy with traditional tissue biopsy. They observed a high consistency between the two, which further supports ctDNA as a non-invasive and real-time screening tool. Lastly, BISCAY’s study model could also positively inform biomarker-based multi-arm clinical trial design.

CheckMate 9ER: the promise of a novel immune-based combination in renal cell carcinoma

Cristina Suárez, Clinical Investigator & Medical Oncologist, Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group (PI: Joan Carles).

Results of the CheckMate 9ER open-label, randomized, phase III study (9) directed by Toni K. Choueiri, Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology (Boston, MA, USA), and co-authored by VHIO’s Cristina Suárez, evaluated the efficacy of first-line immunotherapy with nivolumab plus targeted therapy with cabozantinib versus sunitinib in patients with previously untreated advanced clear cell renal cell carcinoma (ccRCC).

In this multicenter study, performed in 125 cancer centers, urology centers and hospitals across 18 countries, including VHIO and our Vall d’Hebron University Hospital (HUVH), patients were randomly assigned to receive first-line immunotherapy with nivolumab plus targeted therapy with cabozantinib, or sunitinib, until disease progression or toxicity. The primary end point of this investigation was progression-free survival with secondary end points including overall survival and objective response.

The CheckMate 9ER Investigators showed patients who received the nivolumab and cabozantinib combination had significantly better progression-free and overall survival, and a greater likelihood of response compared with those who were assigned to sunitinib. These promising findings point to a potential new therapeutic avenue for this patient population.


Advancing insights into the immune cell and tumor milieu

The immune microenvironment as a driver of disease progression in chronic lymphocytic leukemia

Francesc Bosch, Principal Investigator, Experimental Hematology Group.

Advancing insights into the underlying mechanisms that drive disease progression in chronic lymphocytic leukemia (CLL), results of a study (10) directed by VHIO’s Francesc Bosch suggest that dynamic clonal evolution is not the main culprit. Pointing to the interaction with the immune microenvironment as a key influencer, this research sheds light on why some patients progress on treatment, while others do not.

The investigators performed genetic and immunological longitudinal analysis pairing primary samples from untreated CLL patients with clinical progression, with sampling performed at the time of diagnosis and progression, and from patients with stable disease at diagnosis and long-term asymptomatic follow-up.

As the first comprehensive longitudinal analysis of the genetic and immunological processes implicated in CLL progression, results indicate that alterations in the immune microenvironment are highly significant. They assessed the changes occurring from diagnosis to clinical progression that were not associated with the passage of time but differed among patients with progressive disease compared with those with stable CLL.

Data showed that patients with progressive disease had a greater accumulation of terminally exhausted CD8+ T cells, which can be induced by interleukin 10 (IL-10) cytokine secreted by leukemic cells, and increased expression of some immune inhibitory receptors. All these changes lead to a more rapid deterioration of the immune system; reducing its capacity to hone in on and attack malignant cells.

In concordance with previous studies, these analyses showed that genetic alterations do not explain disease progression since they occurred randomly, and in both groups. Instead, the changes in immune cells reduce their capacity to recognize and kill cancer cells, and the alterations in cancer cells empower them to dodge the immune surveillance of tumors. These results could provide a rationale for the use of early immunotherapeutic intervention to help prevent or stall disease progression.

Exploring immune microenvironment dynamics during HER2-targeted treatment in breast cancer

Paolo Nuciforo, Principal Investigator, Molecular Oncology Group.

The host immune system assumes an important role in HER2-positive breast cancer (HER2+ BC). Around half of these tumors have more than 10% of stromal tumor-infiltrating lymphocytes (sTILS), which associates with better survival in both HER2+ early and advanced breast cancer, as well as higher complete response rates after neoadjuvant anti-HER2-based chemotherapy. These immune cells therefore determine prognosis and might contribute to the efficacy of targeted treatments.

But the composition, localization and functional orientation of these cells within the tumor microenvironment the dynamics at play during anti-HER2 treatment, remain largely unknown. Research directed by VHIO’s Paolo Nuciforo sought to decipher changes in the tumor-immune contexture by assessing sTILs during neoadjuvant treatment with lapatinib, a HER2 tyrosine kinase inhibitor, combined with trastuzumab targeted therapy in patients with early-stage HER2+ BC in the phase II PAMELA trial.

Findings of this study (11) showed that sTIL levels increased after two weeks’ HER2 inhibition in HER-negative disease and the HER2-enriched subtype. Further, their immune contexture analysis revealed that immune cells spatially interacting with cancer cells have the strongest association with response to anti-HER treatment.

This research illuminates the importance of considering the tumor immunosuppressive microenvironment -- a key factor in response to immune checkpoint blockade and adoptive T-cell transfer therapies -- in the design and development of future strategies aimed at more effectively combating early-stage HER2+ BC.


The seeking out and application of robust biomarkers

RAD51 as a biomarker of homologous recombination deficiency & predictor of clinical outcomes in patients with triple-negative breast cancer

Violeta Serra, Principal Investigator, Experimental Therapeutics Group.

Based on DNA repair functionality, the RAD51 assay, pioneered and developed in-house by VHIO’s Violeta Serra’s team, has been proven to complement genomic testing in clinical practice. This was reaffirmed in 2021 for prostate cancer as evidenced by results of biomarker analysis (12) from the TOPARP-B study co-led by VHIO’s Joaquin Mateo (PI: Prostate Cancer Translational Research Group).

Biomarker analysis from the GeparSixto randomized clinical trial (13), directed by Violeta, has validated RAD51 as a clinically relevant biomarker of homologous recombination-mediated DNA repair deficiency, and a predictive tool for selecting patients with primary triple-negative breast cancer who would most likely respond to treatment with platinum-based neoadjuvant chemotherapy.

Patients enrolled in the GeparSixto study received treatment with neoadjuvant non-pegylated liposomal doxorubicin plus paclitaxel with or without carboplatin. Results from their biomarker analysis demonstrated that the patients who benefited most from carboplatin were those with tumors with homologous repair deficiency by RAD51.

This study supports the clinical validity of their RAD51 assay as a functional test and an independent predictive biomarker of response to carboplatin in untreated triple-negative breasts cancer. Building on the positive results of earlier studies across other tumor types, these latest findings point to the future incorporation of RAD51 in the clinic.

Clinically qualifying predictive biomarkers of response to PARPi in prostate cancer patients

Joaquin Mateo, Principal Investigator, Prostate Cancer Translational Research Group.

PARP inhibitors (PARPi) are approved for treating advanced prostate cancers with various defective DNA repair genes, although not all patients derive the same benefit from this targeted therapy. Research led by Johann de Bono, The Institute for Cancer Research, Royal Marsden NHS Foundation Trust (London, UK), alongside VHIO’s Joaquin Mateo -also co-authored by Violeta Serra- sought to clinically qualify predictive biomarkers of response to this class of molecularly stratified therapy.

Aimed at refining the predictive biomarker suite for patient stratification, the investigators analyzed samples from the aforementioned TOPARP-B phase II trial, results of which published in 2020, with Joaquin as a Co-senior author (14). The results from this subsequent study (12) have now revealed a group of ‘super-responders’. Findings showed that patients with complete BRCA2 deletions responded exceptionally to PARPi with high and durable responses, and advanced insights into which patients carrying PALB or ATM mutations might also benefit from this therapy.

These data may enable the fine-tuning of patient stratification in clinical practice, and the more precise identification of those who could benefit from this class of targeted therapy, based on the molecular specificities of their respective disease.

As already highlighted, (see previous sub-section), this study also demonstrates how the RAD51 assay can help to complement genomic testing in clinical practice, also in prostate cancer, by identifying alterations in the BRCA gene, as well as PALB2 mutations; discriminating between biallelic and monoallelic in the latter. This is particularly relevant since this research has also shown that only those patients with biallelic PALB2 mutations benefit from treatment with PARP inhibitor olaparib.


Combating cancer resistance, progression and disease recurrence

Busted: a driver of adaptive resistance to therapies targeting KIT mutations in gastrointestinal stromal tumors

César Serrano, Principal Investigator, Sarcoma Translational Research Group.

Over recent years, much progress has been made in more effectively treating gastrointestinal stromal tumors (GIST) thanks to the advent of a new generation of more potent and ‘smarter’ inhibitors that target the KIT proto-oncogene and dysregulated platelet-derived growth factor receptor (PDGFR). As an example, the tyrosine kinase inhibitor imatinib has shown clinical benefit in around 80-85% of patients with advanced GIST. However, these patients will unfortunately and inevitably develop secondary resistance.

The specific molecular events that ultimately lead to the adaptive resistance of GIST to the current array of agents that target KIT/PDGFRA mutations remain elusive and represent a major challenge in improving outcomes for these patients. Findings from a study (15) led by VHIO’s César Serrano have illuminated the possible causes of resistance by unmasking the E3 ubiquitin ligase Atrogin-1 (FBXO32) protein as a mediator of resistance to KIT-targeted inhibition in GIST.

The investigators, including Joaquin Arribas (PI: VHIO’s Growth Factors Group), assessed clinically representative in vitro and in vivo GIST models and GIST patients’ samples. Using NGS and GIST-specific gene panels, they studied multiple genes and associated pathways in KIT GIST, and discovered that FBXO32, is one of the most critical genes differentially expressed in GIST upon inhibition of KIT and related pathways, irrespective of the type of KIT mutation.

Using different preclinical models, they observed that KIT-targeted inhibition leads to a significant increase in FBXO32. This overexpression is a specific survival mechanism of GIST cells, enabling the adaptation to KIT-directed inhibition by apoptosis evasion via cell quiescence.

Currently, there are no specific inhibitors targeting this protein, calling for the development of novel agents. Signposting next step directions, the authors proposed that potential new therapies could be used in combination with imatinib as a more effective treatment strategy. Performing in vitro and in vivo studies they assessed the efficacy of combining imatinib with the TAK-243 small-molecule inhibitor of the ubiquitin activating enzyme.

This novel therapeutic pairing effectively halted adaptation to treatment mediated by FBXO32 and led to a significant increase in cancer cell death. This strategy could help to potentiate currently available therapies in this patient population.

First-in-class targeted therapy as a promising new contender against advanced cholangiocarcinoma

Teresa Macarulla, Principal Investigator, Gastrointestinal & Endocrine Tumors Group.

Aimed at improving outcomes for previously treated patients with unresectable or metastatic cholangiocarcinoma, whose tumors express an isocitrate dehydrogenase 1 mutation (IDH1), the phase III multicenter, randomized ClarlDHy clinical trial assessed the performance and safety of ivosidenib, a first-in-class targeted inhibitor of IDH1, that is already approved for the treatment of acute myeloid leukemia in some patients with this genetic variant.

Results from this double-blind, placebo-controlled study (16) reported the final overall survival and safety profile of ivosidenib in patients with IDH1-mutated CCA whose disease had progressed on one or two previous treatment lines with chemotherapy. By putting ivosidenib to the therapeutic test, the investigators sought to open up a new, more effective and less toxic treatment avenue to target this highly aggressive tumor type.

The ClarlDHy Investigators, led by Andrew X. Zhu, Massachusetts General Hospital Cancer Center, Harvard Medical School (Boston, USA), including VHIO’s Teresa Macarulla, showed that ivosidenib numerically improved overall survival compared with placebo, despite a high crossover rate, maintained quality of life, and was well tolerated.

Moving forward, this targeted therapy could potentially respond to the unmet need for new therapies to more effectively combat IDH1-mutated CCA. Future studies will aim at achieving a deeper understanding of mechanisms of resistance, and additional translational studies are already under way to investigate disease relapse using circulating tumor DNA (ctDNA) analysis.

COSMIC-311: delivering a new standard of care for patients with thyroid cancer

Jaume Capdevila, Clinical Investigator and Medical Oncologist, Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla).

The double-blind phase III COSMIC-311 study evaluated the efficacy and safety of targeted therapy, cabozantinib, versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RAIR DTC) who had progressed during/after prior VEGFR-targeted therapy for whom there is no standard of care.

The interim results of this pivotal study (17), led by Marcia S. Brose, Abramson Cancer Center, University of Pennsylvania (PA, USA), and co-authored by VHIO’s Jaume Capdevila, achieved the primary endpoint of progression-free survival in all randomized patients including those who had previously received lenvatinib, and cabozantinib showed clinical and statistical improvements over placebo, with no unexpected toxicities.

The final data of COSMIC-311 were subsequently presented by Jaume Capdevila during ESMO 2021. Results confirmed the superior efficacy and manageable safety profile of cabozantinib, as previously evidenced, with improved progression-free survival, irrespective of prior VEGFR-targeted therapy. Cabozantinib achieved a striking 80% reduction in the risk of disease progression in these patients.

Based on these results, the U.S. Food and Drug Administration (FDA), granted approval of this therapy as a new standard of care for this patient population in September 2021. The European Medicines Agency (EMA) recently followed suit with recommended approval of cabozantinib for the treatment of patients with locally advanced or metastatic DTC, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy (March 2022).

These regulatory approvals represent new hope for these patients who are in particular need of more effective treatment options.

PARPi prevents disease recurrence in BRCA-mutated high-risk, early-stage breast cancer

Judith Balmaña, Principal Investigator, Hereditary Cancer Genetics Group.

BRCA mutations are found in approximately 5% of breast cancer patients. Around 55-65% of women with a BRCA1 mutation, and approximately 45% with a BRCA2 mutation will develop breast cancer before the age of 70. Despite the many advances in developing more potent, targeted treatments, many patients with high-risk disease will unfortunately suffer relapse.

The OlympiA interventional Phase III study, directed by Andrew Tutt, Institute of Cancer Research and Kings College London (London, UK), and co-led by VHIO’s Judith Balmaña, aimed at extending the personalized and targeted promise of olaparib to patients with early-stage, primary, high-risk HER2-negative breast cancer and a germline BRCA1/2 mutation (gBRCAm), to improve clinical outcomes as well as prevent disease recurrence.

Selected to first outing during ASCO 2021, and published in parallel (18), data showed that targeted treatment with olaparib achieved a significantly superior reduced risk of disease relapse compared with the control group. Regarding the recurrence of invasive disease, analysis at three years revealed that over three quarters of patients in the placebo arm and over 80% of those receiving olaparib showed no relapse. Furthermore, as an orally administered therapy with low-level toxicity, this agent promises improved quality of life for these patients. Showing that patients with early-stage high-risk breast cancer with an inherited BRCA1/2 mutation can be more effectively treated with targeted therapy, these results were heralded as potentially practice-changing.


The promise of powerful antibody-drug conjugates

Expanding the therapeutic arsenal against metastatic breast cancer

Cristina Saura, Principal Investigator, Breast Cancer & Melanoma Group.

Presented at ESMO 2021, Cristina Saura revealed primary outcomes of the phase III TULIP study. This multi-center, open-label randomized clinical trial compared the efficacy and safety of the antibody-drug conjugate (ADC), [Vic-] trastuzumab duocarmazine, to physician’s choice in the treatment of patients with HER2-positive, progressive metastatic breast cancer (MBC) who had received at least two previous lines of therapy or ado-trastuzumab emtansine treatment in the metastatic setting.

Conducted at 89 sites, including VHIO, the study’s primary endpoint was progression-free survival. The investigators reported a statistically significant improvement over physician’s choice treatment, and observed a trend toward better overall survival for patients treated in the experimental arm.

While these results show promise, adverse events were reported. Moving forward, these manageable events will need to be considered in the development of this next generation ADC as a contender in the treatment of these patients.

Ringing in an antibody-drug conjugate in early breast cancer

Mafalda Oliveira, Clinical Investigator and Medical Oncologist, Breast Cancer & Melanoma Group (PI: Cristina Saura).

The first results of a window of opportunity trial, SOLTI- 1805 TOT-HER3, were presented at ESMO 2021. Co-led by VHIO’s Mafalda Oliveira and directed by Aleix Prat (Hospital Clínic Barcelona), TOT-HER3, is the first study to evaluate the HER3 directed antibody-drug conjugate (ADC), patritumab deruxtecan, in patients with early hormone-sensitive HR-positive/HER2-negative breast cancer. Prior to this clinical trial, this ADC had only demonstrated anti-tumor activity and a tolerable safety profile in patients with heavily pretreated metastatic high or low HER3 expression levels.

Preliminary results from the first patients included in this trial showed tumor reduction in just under half of cases. Over half of these enrolled patients showed increased immune infiltration and reduced tumor cellularity with just a single shot of the drug. In almost one out of two cases, this therapy achieved tumor shrinkage and even the disappearance of disease. As encouragingly, the treatment was tolerable and the safety profile was consistent with that previously reported for this ADC.

These promising findings could ultimately translate in benefits for patients with newly diagnosed early HER2-negative breast cancer.

DESTINY-Breast03: promising a new standard of care for HER2-positive metastatic breast cancer

Javier Cortés, an Associate Translational Investigator at VHIO.

Headlining at ESMO 2021, results from the DESTINY-Breast03 phase III trial were presented by lead investigator Javier Cortés, Associate Translational Investigator at VHIO. This study compared the efficacy and safety of a new-generation HER2-directed antibody-drug conjugate (ADC), trastuzumab deruxtecan-nxki, with the older-generation ADC, trastuzumab emtansine, in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane treatment.

The primary endpoint of this study was progression-free survival (PFS). Over 70% of patients treated with trastuzumab deruxtecan arm in the second line remained without progression or worsening of disease at 12 months, compared to 34% of patients treated with trastuzumab emtansine in standard treatment arm of this study. The data, heralded as spectacular, also showed an objective response rate of almost 80% versus 34% in the trastuzumab emtansine arm, further supporting the striking clinical activity of this new-generation ADC.

Based on the striking results from the previous phase II DESTINY-Breast01 trial, co-authored by Cristina Saura (19), Principal Investigator of our Breast Cancer Group, and Javier Cortés, the U.S. Food and Drug Administration (FDA) granted trastuzumab deruxtecan Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.

Of note, further to the reported DESTINY-Breast03 data, new clinical practice guidelines for metastatic breast cancer were developed and published (20) by eminent leaders in this field, including Cristina and Javier, outlined that this new-generation ADC may be considered as second-line therapy in regions where the drug is available.

DESTINY-CRC01: exploratory biomarker analysis in tumor and liquid biopsy

Elena Élez, Medical Oncologist and Clinical Investigator, Gastrointestinal and Endocrine Tumors Group (PI: Teresa Macarulla).

Reported at ASCO 2021, results of the phase II, multicenter, open-label DESTINY-CRC01 trial (21) showed that treatment with the antibody-drug conjugate (ADC), trastuzumab deruxtecan-nxki, produced durable responses in patients with previously treated HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with that reported in previous trials assessing this therapy.

The DESTINY-CRC01 Investigators, including VHIO’s Elena Élez, performed subsequent exploratory biomarker analysis by tumor and liquid biopsy to seek out potential mechanisms of resistance and response for the more precise matching of patients to this therapy. The results were presented by lead author Salvatore Siena, Università degli Studi di Milano (Milan, Italy) at ESMO 2021.

Biomarker data in paired ctDNA samples collected at baseline and disease progression from patients enrolled in this trial indicate that antitumor activity correlates with baseline HER2 expression or amplification in both tumor and liquid biopsy. In the paired ctDNA samples by liquid biopsy that were collected at the beginning of the study and during disease progression, acquired alterations were observed in several genes, but none were common across patients.

Further studies assessing the potential mechanisms of resistance and patient selection for this therapy in patients with HER2-positive metastatic colorectal cancer are warranted.


Dynamic designs, approaches, tools and platforms

Since VHIO incorporated in-house BEAMing liquid biopsy RAS biomarker technology in 2015, the first academic test center to do so, our teams have made great progress in validating and developing liquid biopsy and Droplet Digital PCR Bio-Rad technologies for the more effective, less invasive ‘policing’ of cancer over time, in real time.

Illustrative of these efforts are the following two VHIO research developments that also made headlines in 2021:

Immune cells in cerebrospinal fluid: predictors of response to immunotherapy against brain metastasis

Joan Seoane, Co-Director of Preclinical & Translational Research, Principal Investigator, Gene Expression & Cancer Group, and an ICREA Research Professor.

Results from previous studies (22),(23) led by Joan Seoane and other groups, have shown that cerebrospinal fluid can provide vital insights into the genomic characteristics of brain tumors and therefore be used as a minimally invasive liquid biopsy. Spurred by these findings, the investigators sought to establish whether they could effectively characterize the tumor microenvironment in brain metastasis.

By analyzing immune cells infiltrating cerebrospinal fluid for the characterization of the tumor microenvironment in brain metastases, latest research directed by Joan (24) confirms that these cells recapitulate the characteristics of those detected in brain metastases and could act as novel and non-invasive biomarkers to predict patient responsiveness to immune-based therapies.

Immune checkpoint inhibitors (ICIs), including anti-PD1, anti-PD-L1, and anti-CTLA4, have shown significant clinical benefits in patients with progressive or metastatic solid tumors, including some brain metastasis. Notably, these immune-based therapies have improved outcomes for some of those suffering from lung cancer and melanoma. Together, these tumor types along with breast cancer, are three common malignancies that lead to brain metastases.

One of the major challenges is that new lesions can differ immensely from the primary tumor, and thus respond in a different way to immune-based therapies. While some patients benefit from treatment with ICIs, the majority do not. To predict response to these therapies necessitates the characterization of tumor specimens. Due to the anatomical location of brain tumors and the risk of surgical procedures, accessing samples from brain malignancies is challenging.

Joan’s team analyzed patients’ samples and assessed the immune cells present in the brain metastases. In parallel, they performed immune cell profiling of cerebrospinal fluid to identify which cell types were present and compared them to those obtained from the metastatic lesions. They identified the T cells that recognize tumor cells, and those that are active in treatment.

By characterizing the individual sequences of immune cells the investigators established which cells are attacking the tumor, discerning how they evolve over time. This pioneering approach could help to more precisely guide clinical decision making in treating these patients with immune-based therapeutic strategies.

VHIO’s suite of cutting-edge technologies: incorporating Guardant Health’s liquid biopsy test

Ana Vivancos, Principal Investigator, Cancer Genomics Group.

Announced at the beginning of 2021, VHIO’s Cancer Genomics Group, led by Ana Vivancos, has now incorporated the Guardant Health liquid biopsy. As the first cancer research center to do so in Europe, this avant-garde platform provides complete genomic results in all solid tumors from a simple blood test in seven days and will therefore help to overcome the limitations associated with traditional tissue biopsy.

Guardant360 CDx technology -- the first liquid biopsy test for comprehensive genomic profiling to have received approval from the U.S. Food and Drug Administration (FDA) – will facilitate the non-invasive detection of an increasing number of mutations for the more precise selection of therapies matched to the molecular specificities of each individual patient’s disease.

This tool will also enable VHIO’s clinical investigators and medical oncologist to identify and select those patients who may be candidates for enrollment in clinical trial studies performed at our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, directed by Elena Garralda.

Integrating this new technology into VHIO’s expanding suite of cutting-edge platforms will further spur our dedicated efforts aimed at developing and advancing next generation therapies and precise diagnostics in precision oncology. Watch this space!

Spearheading next generation clinical trials: Cancer Core Europe’s design and development of data-rich, adaptive studies in oncology

Elena Garralda, Principal Investigator, Early Clinical Drug Development Group, and Director of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – Caixa Research.

Incorporating experts from the seven European comprehensive cancer centers belonging to the Cancer Core Europe (CCE) Consortium, including VHIO, along with an additional four non-CCE partners, the EU-funded, multi-site EU Horizon 2020-funded project CCE Building Data Rich Clinical Trials (CCE-DART) officially launched in 2021.

As I mentioned in last year’s report, CCE-DART, led by VHIO’s Elena Garralda, seeks to become a groundbreaking example in driving a novel generation of clinical trials in the current era of precision oncology by developing interconnected tools to reduce the current complexity of investigator-initiated trials. This project also aims at better guiding clinical decision-making by integrating cutting-edge digital technologies and platforms.

To overcome the rigidity and limitations of traditional randomized controlled trials that do not allow for the ‘real time’ and necessary adaptation in tune with the rapid pace of cancer discovery – especially in the academic setting, novel clinical trial designs promote the optimization of biomarker-drug co-development towards more precisely tailoring therapies to each disease setting, each individual patient.

CCE-DART investigators will spur the design and development of a new generation of dynamic data-rich studies in oncology. Building on the CCE-developed Basket of Baskets (BoB) investigator-initiated and adaptive trial which launched in 2018, CCE-DART will further enhance BoB’s harmonized, molecular multi-tier profiling platform to more precisely match patients to novel anti-cancer medicines. In parallel, they will continue to develop multiple treatments in genomically-selected populations.

By introducing new tools (or adapting existing ones) the project also seeks to elevate the management and decision-making of clinical studies to the digital age, and ultimately represent a groundbreaking example for driving a new generation of clinical trials in by leveraging novel technologies within existing clinical structures.

Common infrastructures and the wealth of experience gained through CCE sites’ running of innovative academic studies will help the project partners to deliver on the four key objectives. Namely, to improve patient enrolment strategies and trial designs, accelerate the use of novel health technologies in the clinical setting, optimize clinical trial data management and analysis, and globalize the results of the project by promoting transparency of investigator-initiated studies.

This project has received funding from the European Union’s Horizon 2020 framework programme research under grant agreement No: 965397.


Returning briefly to BoB, a new iBASKET therapeutic module was introduced in 2021. Also led by VHIO, this addition will focus on the targeting of fibroblast growth factor (FGFR) genomic alterations present in multiple tumor types. Incorporating four different arms, investigators will assess the anti-tumor activity and efficacy of FGFR inhibitor futibatinib in patients with FGFR-aberrant solid tumors.


CT-based radiomics signatures to predict response to immune checkpoint inhibitors in advanced solid tumors

Raquel Perez-Lopez, Principal Investigator, Radiomics Group.

Research spearhead by Raquel Perez-Lopez has culminated in the development of a new, non-invasive tool to predict response to immune checkpoint inhibitors in patients with solid tumors. This pioneering radiological model is based on the application of artificial intelligence in the assessment of pretreatment computed tomography images of tumors, where associations can be made between these images and molecular profiles correlating with immune response.

Predicting response prior to the administration of anti-PD-1 and PD-L1 immunotherapies, results of this study (25) showed up to 75% accuracy in patients treated at our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, directed by Elena Garralda.

By providing reliable predictive scoring, this non-invasive approach promises the more precise identification of those patients who would be most likely to benefit from immune checkpoint inhibitor monotherapy and enables a closer tracking of disease progression and response to treatment, over time. This tool can also capture tumors in their entirety as opposed to limited pictures obtained from the particular biopsy site which do not accurately reflect tumor heterogeneity.

The authors conclude that the integration of multidimensional data including radiomics, clinical variables and genomic characterization may be key to optimizing immune checkpoint inhibitor treatment selection toward ultimately improving survival and quality of life of cancer patients. Further, while their predictive radiomics signature shows promise for anti-PD1/PD-L1 patient selection, additional testing in other cohorts as newer immunotherapies emerge will be required.

PIPO: a web-based tool for patient selection in early phase clinical trials

VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – Caixa Research: a leading reference in early clinical drug development & clinical trials in oncology.

Research (26) headed by VHIO’s Elena Garralda, Principal Investigator of VHIO’s Early Clinical Drug Development Group & Director of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM)–Caixa Research, alongside co-corresponding author, Ignacio Matos, a Phase I Investigator of the same group, has led to the development a user-friendly online prognostic calculator, PIPO.

This VHIO Clinical Program core study, counting on the expertise of several other clinical investigators and medical oncologists at our Institute including Rodrigo Dienstmann, Principal Investigator of our Oncology Data Science–OdysSEy Group, was designed to tackle the well described challenge of patient selection in early phase clinical trials.

Using a training cohort with consecutive patients from our UITM–Caixa Research, the researchers built a prognostic model to predict overall survival outcomes of patients to be enrolled in phase I studies with immune checkpoint inhibitors or targeted therapies based on clinical parameters assessed at baseline.

Results of this study demonstrate that the PIPO calculator is a feasible, objective, and user-friendly interactive tool to gauge specific survival probabilities for each patient prior to enrolment in a phase I trial and is useful for both treatment types.


Spin-off successes

Peptomyc’s Omomyc-based therapy put to the clinical test

Laura Soucek, Co-Director of Preclinical & Translational Research, Principal Investigator, Models of Cancer Therapies Group, an ICREA Research Professor, and Co-Founder & Chief Executive Officer of VHIO-born spin-off Peptomyc S.L.

Co-founded back in 2014 by VHIO’s Laura Soucek, CEO of the enterprise, and Marie-Eve Beaulieu, Chief Scientific Officer (CSO) of the company, VHIO-born spin-off Peptomyc received approval from the Spanish Agency of Medicines and Medical Devices for conducting clinical trials in Spain (AEMPS), to initiate the first-in-human Phase I/IIa clinical trial with its first compound – a disruptive Myc inhibitor, Omomyc (OMO-103).

Building on the proven preclinical efficacy and safety of the Omomyc cell-penetrating mini-protein in mouse models (27), and Peptomyc’s company’s successful development of anti-Myc peptides for the treatment of several tumor types, this latest milestone, celebrated in March 2021, represents a greatly anticipated leap into the clinical research setting and an important step forward in becoming the first ever clinically viable and direct inhibitor of Myc – a protein implicated in the formation of most tumor types.

MYC has been considered an ‘undruggable’ cancer target for many years. Laura’s group has previously shown that Myc blockade has an excellent therapeutic effect in several mouse models, with mild side effects that are well tolerated and reversible. Now that Laura and her Peptomyc team have received approval to initiate their early phase clinical trial, they can further progress in testing the safety and efficacy of this Omomyc-based therapy for the benefit of cancer patients.

Their Phase I/IIa Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours - MYCure (NCT04808362), led by VHIO’s Elena Garralda, Director of our Research Unit for Molecular Therapy of Cancer (UITM) –CaixaResearch and Principal Investigator of Early Clinical Drug Development at our Institute, is now underway.


As an aside, I would like to highlight a superb review (28) co-authored by Laura Soucek and Jonathan R. Whitfield, Senior Investigator of her Models of Cancer Therapies Group, that transports us on the long and often rocky road in bringing a Myc inhibitor closer to the clinic.

Sharing their personal views and hopes for the future, as well highlighting the scientific breakthroughs and multiple strategies aimed at successfully targeting Myc, they salute the extraordinary efforts of all the researchers focused on developing treatment for a target long deemed ‘undruggable’. The final haul towards a first Myc inhibitor in the clinic? Based on this this review, inhibiting one of the most wanted targets in cancer therapy might be within reach.


Mosaic Biomedicals’ MSC-1: transitioned to the clinic

Joan Seoane, Co-Director of Preclinical & Translational Research, Principal Investigator, Gene Expression & Cancer Group, an ICREA Research Professor, and Co-Founder of Mosaic Biomedicals.

VHIO’s Joan Seoane and his Gene Expression & Cancer Group previously established the role of leukemia inhibitor factor (LIF) in oncogenesis as a promoter of cancer progression by regulating the tumor microenvironment and inducing self-renewal in tumor-initiating cells. This research culminated in the development of MSC-1, a therapeutic LIF neutralizing antibody. MSC-1’s transition to the clinic and translation into benefits for cancer patients promises an important addition to the current arsenal of powerful anti-cancer weaponry.

Joan co-founded VHIO-born spin-off Mosaic Biomedicals in 2012 for the design and development of this novel compound. In 2016, Mosaic merged with Northern Biologics Inc. (Toronto, Canada), and Northern-Mosaic announced the global acquisition of clinical-stage MSC-1 (now AZD0171) by MedImmune/AstraZeneca in 2020.

The phase II clinical trial of AZD0171 (in combination with durvalumab and chemotherapy) in solid tumors (NCT04999969) has initiated patient recruitment.


Setting out: spin-off ONIRIA Therapeutics to counteract cancer resistance and combat disease relapse

Héctor G. Palmer, Principal Investigator, Stem Cells & Cancer Group, Co-Founder and Chief Scientific Officer, ONIRIA Therapeutics.

Created in 2021, and officially launched as this scientific report goes to print, a new spin-off, ONIRIA Therapeutics, comprises three co-founding partners: VHIO, the Universidad de Barcelona (UB), and the ICREA Catalan Institution for Research, and is mainly funded by the ”la Caixa” Foundation, Asociación Española Contra el Cáncer – AECC (Spanish Association Against Cancer), and the Instituto de Salud Carlos III – ISCIII (Institute of Health Carlos III).

By modulating cell dormancy to overcome cancer persistence, this spin-off will develop new anti-cancer armory to counteract resistance and prevent disease relapse in patients. Among various ongoing projects, ONIRIA Therapeutic’s most advanced agent is a first-in-class molecule, ONR-001, that allosterically activates the TET2 master epigenetic enzyme, causing tumor cells to enter a dormant state and even die.

ONIRIA has already secured patent protection for its TET2 modulators and demonstrated efficacy in preclinical animal models by showing that ONR-001 promotes and sustains cancer cell dormancy and even causes cell death upon prolonged treatment. The investigators are now evaluating the efficacy of ONR-001 in several hematologic and solid tumor types, honing in on those cancers that are hypermethylated as a consequence of TET2 loss-of-function.

Héctor G. Palmer is ONIRIA’s Chief Scientific Officer, and Esther Riambau, a venture builder, serves as the company’s Chief Executive Officer. The founding team also includes Isabel Puig, a Senior Investigator of Héctor’s group, as the company’s Scientific Advisor for new therapeutic targets; Xavier Barril, an ICREA investigator at UB, and ONIRIA’s Scientific Advisor in computational chemistry; Carlos Galdeano, a Serra Hunter Lecturer Professor and Head of the Protein Degradation Laboratory at UB, who is appointed as its Scientific Advisor in drug discovery.

This pioneering project has also been possible thanks to the additional support received from Agència de Gestió d’Ajuts Universitaris i de Recerca – AGUAR (Agency for Management of University and Research Grants), Fundación FERO (FERO Foundation), and the Fundació Privada CELLEX .


The power of cross-border collaboration in precision oncology

In addition to our participation Cancer Core Europe, we also belong to several other important collaborations and partnerships. 2021 celebrated the launch of several new projects including the PERSIST-SEQ international Consortium:

PERSIST-SEQ is a five-year public-private partnership to provide the cancer research community with a new gold standard workflow for single-cell sequencing by developing and validating best practices as well as generating and analyzing high-quality FAIR data. Led by Principal Investigator Alexander van Oudenaarden, Hubrecht Institute (Utrecht, The Netherlands), PERSIST-SEQ connects 16 partners and is co-directed by the Oncode Institute (Utrecht) and AstraZeneca.

Funded by the Innovative Medicines Initiative (IMI), this project represents an important step forward in developing smarter, standardized and reproducible approaches to effectively predict, target, and combat drug-resistance in cancer. Leading experts in cancer modelling and the development of single-cell sequencing technologies will advance insights into the complexity and heterogeneous response of single-cell-derived persisters to anti-cancer therapies.

Led by Héctor G. Palmer, our investigators will provide clinical expertise and patients’ samples (pre, post and on-treatment), develop sophisticated mouse models linked to clinical trials, and direct one of the defined work packages on single-cell acquisition from models of tumor plasticity.

PERSIST-SEQ receives funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 101007937.


Strengthening our programs and supporting VHIO’s research talents

As our Institute goes from strength to strength, and seeks to further develop its research lines and projects based on strategic directions, we continue to expand our scientific faculty. 2021 celebrated the incorporation of two new VHIO team leaders:

Jose A. Seoane, Principal Investigator, Cancer Computational Biology Group.

Jose A. Seoane joined us to establish and lead VHIO’s Cancer Computational Biology Group which focuses on leveraging epi(genetic) cancer datasets to unmask the molecular mechanisms implicated in cancer initiation, progression, drug resistance and metastasis.

Jose’s group aims at advancing insights into the role of chromatin regulatory elements in treatment response and metastasis, identifying new epigenetic biomarkers of drug response, and potentiating anti-cancer medicines by combining epigenetic therapies with other agents.

Lara Nonell, Head, Bioinformatics Unit.

Expanding our Core Technologies Program, Lara Nonell has set up VHIO’s Bioinformatics Unit to implement state-of-the-art pipelines and develop tools for the analysis and visualization of different omics datasets, including publicly available datasets.

Her team seeks to integrate and apply advanced bioinformatics approaches to identify and validate biomarkers for cancer diagnostics, generate computational models to incorporate multi-omics data using classical or cutting-edge machine learning techniques, and establish collaborative research with VHIO groups to promote the use of advanced computational methods for data analysis, visualization and interpretation.

Susana Aguilar, Head, VHIOTECA Unit.

Our VHIOTECA Unit was created in 2021 to support investigators for the obtention, registration and preservation of biological samples other than tumoral tissue (plasma, feces, saliva) from cancer patients, and facilitate the use of these samples in research projects. Joining our other transversal clinical trials core services, VHIOTECA’s team is headed by Susana Aguilar and comprises clinical research oncology nurses specialized in specific tumor types, sample managers, and support technicians for sample logistics and database creation/maintenance.

Providing an optimal structure for the dynamization of circuits, this Unit seeks to consolidate, develop and improve existing circuits and processes, and help VHIO researchers to set up new projects and foster new collaborations requiring these types of samples. Spurring studies into the microbiome during tumor development and progression, especially in colorectal cancer, they will also focus on the collection, genomic and molecular analysis of stool samples. VHIOTECA also compliments our Molecular Prescreening Program, which is also coordinated by Susana alongside Jenifer González, a Research Support Technician.


Left to right: VHIO Academy Co-Chairs, Elena Élez, Clinical Investigator and Medical Oncologist, Gastrointestinal & Endocrine Tumors Group, Maria Abad, Principal Investigator, Cellular Plasticity & Cancer Group, and Clara Caminal, Head of the Academy.

Launched this year, the VHIO Academy, manages, integrates and disseminates training opportunities in cancer research, educational initiatives for all VHIO personnel as well as programs tailored to patients and members of our community. Directed by Co-Chairs, Elena Élez and Maria Abad, and headed by Clara Caminal, its main objective is to provide a range of activities aimed at the career development of our faculty and foster a training environment of excellence.

Just some of these programs include institutional fellowships to attract and retain research talents in oncology, continuous learning opportunities such as complementary courses, workshops, seminars and educational events.

In 2021 our first institutional doctoral fellowships call included five four-year FPI-Severo Ochoa grants for national and international young researchers to carry out their doctoral thesis research at our Institute. Associated with our recent accreditation as a Severo Ochoa Center of Excellence, these opportunities are within the framework of the EU Pre-doctoral training contracts (FPI) 2021, and supported by the Spanish Ministry of Science and Innovation.


Honoring the life and legacy of the father of precision medicine in oncology

José Baselga, MD, PhD (1959-2021): a global trailblazer in oncology, pioneer of translational cancer research, and VHIO’s founder and first director.

My Foreword to last year’s report included my personal tribute to VHIO’s founder and first director, José Baselga, who very sadly died at the age of 61 on 21 March, 2021. While José’s untimely passing will continue to represent an unfillable void in cancer research treatment and care, he leaves a tremendous legacy for the scientific community; one that will continue to inspire present and future generations of cancer researchers and clinical investigators.

Reflective of the scale of our collective loss, tributes in his memory published in numerous leading scientific journals of excellence. Tragically, these included the first obituary published in Cancer Discovery (29), a journal of the American Association for Cancer Research (AACR), for which he served as a co-founding Editor-in-Chief. Several other touching tributes dedicated to José’s memory (30),(31),(32), also captured his qualities as an iconic leader and chaptered his illustrious career trajectory devoted to improving outcomes for cancer patients worldwide.

In José’s honor two special awards have recently launched. One of our Institutional Supporters, the Fundación FERO, that he founded in 2001, announced its Dr. Baselga Award to further promote translational research in oncology. This accolade will prize translational research of excellence carried out at research institutes in Spain by investigators of any nationality. In addition to FERO’s Annual Awards for Translational Research, this grant will further spur the translation of scientific discovery into clinical benefits for our patients.

The AACR-AstraZeneca Career Development Award for Physician-Scientists, honoring his extraordinary life and scientific legacy, will foster the careers of promising physician-scientists and support impactful clinical research with the potential to markedly improve patient outcomes.

On a related note, a superb documentary supported by AstraZeneca, José Baselga: Cancer’s Fiercest Opponent, beautifully chapters his life, career, charismatic persona and all the qualities that made him a visionary in oncology and a truly dedicated, generous mentor of countless talents in our field. This one-hour tribute, covering many defining periods of his life and illustrious career, also includes precious footage and family photos, personal reflections, memories and lesser-known facts that José’s wife, Silvia, and their four children Marc, Clara, Alex, and Pepe, so generously share with the audience.

Alongside other colleagues who had the privilege of working with José and knowing him as an extraordinary person impassioned by everything he did, I am truly honored to have participated in this outstanding documentary.

At VHIO, we strive to honor José Baselga’s legacy by applying the same dedication, determination, collaborative spirit and fight in combating cancer.

He will never be forgotten.

The Last Word

As VHIO's Director, I am extremely fortunate to lead and work with our many research talents and dedicated healthcare professionals in oncology. Without our multidisciplinary, translational and clinical teams, national and international collaborations and partnerships, coupled with our unified determination to solve cancer sooner, our Institute would cease to exist.

That same sustained devotion and belief is also shared in equal measure by our amazing Institutional Supporters and Patrons – the Generalitat de Catalunya, Fundació Privada CELLEX, Fundación FERO, ”la Caixa” Foundation, and the Fundación BBVA as well as VHIO's many other funding entities, agencies, and individuals. They all share the same sustained devotion and intense desire as we do: to reduce the devastating burden that this disease has on society.

Illustrated by the many research highlights and developments chaptered in the pages that follow, we continue to drive, ‘crystalized’ progress against cancer.

By doing what we do best, namely turning challenges into opportunities, I believe that we will report bigger success in more effectively targeting and thwarting this disease through 2022 and beyond.

We can, and will, do even better.



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A seal of scientific leadership at global level: VHIO accredited as a Severo Ochoa Center of Excellence (2022-2026)

Announced at the end of 2021, and highlighted by our Director in his Foreword to this year’s Scientific Report, our Institute has been accredited as a Severo Ochoa Center of Excellence. This prestigious distinction is granted within the subprogram of the Spanish Institutional Strengthening of the State Plan for Scientific and Technical Research & Innovation, and recognizes national research centers that demonstrate scientific leadership of excellence and impact at global level.

Conferring reputation and social and scientific recognition, this accreditation is awarded annually, managed and supported by Spain’s State Research Agency* (Agencia Estatal de Investigación - AEI) - a body affiliated with the Spanish Ministry of Science and Innovation (Ministerio de Ciencia e Innovación). Valid for four years, this accreditation is renewable thereafter through re-application for the same rigorous evaluation carried out independently by an international scientific committee of renowned researchers.

From the 2020 call, VHIO is the only newly accredited Severo Ochoa Center of Excellence, alongside the other six re-awarded research centers. Set within the Vall d’Hebron Barcelona Hospital Campus, VHIO is also the first research institute linked to the national healthcare system to have received this distinction.

This accolade reflects our Institute’s important contributions to cancer science and precision medicine in oncology at a global level. It also confirms VHIO’s scientific leadership and proven capacity to advance frontier research, generate high-impact results, as well as attract and retain research talent.


*Supported by the State Agency for Research - Agencia Estatal de Investigación - AEI (CEX2020-001024-S / AEI / 10.13039 / 501100011033).

INTRODUCING VHIO

Who we are and what we do

VHIO's Organigram 2021

In order to translate cancer discovery into real benefits for an increasing number of our patients, we adopt a purely translational, multidisciplinary research model. Organized into three main programs – Preclinical & Translational, Clinical, and Core Technologies, our research focuses on achieving a deeper understanding of the fundamental biology of human cancer, from cellular and molecular biology and genetics through to therapeutics.

Our optimal organizational structure enables VHIO research talents to anticipate and tackle the many unresolved questions that currently hamper efforts aimed at solving cancer sooner.



Championed by VHIO’s Director, Josep Tabernero, our Principal Investigators as well as the Heads of our Transversal Clinical Trials Services, Units and Programs, spearhead efforts aimed at solving cancer sooner. They lead their respective groups and teams to turn obstacles into opportunities, and work tirelessly to resolve current and future challenges in beating this highly complex disease.


VHIO in 2021: Turning 15 and driving continued, ‘crystalized’ progress against cancer during COVID-19 pandemic waves

Josep Tabernero, VHIO’s Director and Head of the Medical Oncology Department, Vall d’Hebron University Hospital – HUVH (Vall d’Hebron Barcelona Hospital Campus).

Under the leadership of Josep Tabernero, the Vall d’Hebron Institute of Oncology (VHIO) has established itself as a comprehensive cancer center of proven excellence internationally and continues to grow from strength to strength. It is thanks to VHIO’s optimal organizational structure and multidisciplinary, translational research model that we continue to anticipate and tackle the many challenges posed by this multifaceted, heterogeneous and hugely complex disease.

This transformative approach was pioneered by José Baselga, our Institute’s founder and first director, who very sadly passed away from Creutzfeldt-Jakob disease (CJD), a rapidly progressing, neurodegenerative disease, at the age of 61 on 21 March, 2021.

From the outset, José had one guiding principle for VHIO. Namely, to seamlessly bridge preclinical and clinical research in order to foster a continuous virtuous cycle of knowledge from bench to bedside and back. This translational approach continues to be at the very core of VHIO’s philosophy and is passionately pursued by our multidisciplinary teams and research talents.

In honor of José Baselga’s incredible legacy, we collectively strive to apply the same dedication and fight in beating cancer, each and every day.

Without the generous support we receive from our Institutional Supporters, public funding, private institutions, companies, and individuals, as well as through International and National Competitive Grants, our Institute would simply cease to exist. We are also truly grateful for the tremendous backing that we continue to receive from our dedicated patrons: the Generalitat de Catalunya, Fundació Privada CELLEX, Fundación FERO, ”la Caixa” Foundation, and the Fundación BBVA.

Just some of their many contributions include the following:

Our public Patron, the Generalitat de Catalunya (Government of Catalonia) – together with the Vall d’Hebron University Hospital (HUVH) – represented by its Departament de Salut (Department of Health), and Departament de Empresa I Coneixement (Department of Industry and Knowledge), has from the very outset been a dedicated supporter of VHIO’s cancer science and medicine.

As a devoted ambassador of VHIO and our various research programs and projects, it has been institutionally and financially supporting us throughout our first decade and now, beyond, with the Catalan Minister of Health as the President of our Board of Trustees.

At ‘home’ VHIO’s translational and multidisciplinary approach to cancer research is greatly facilitated through the connectivity and tremendous collaboration we have with the entire spectrum of oncology professionals at HUVH, the Vall d’Hebron Barcelona Hospital Campus, and the rest of the Catalan Public Health System.

The Catalan Department of Health has played an essential role in integrating VHIO’s research activity into the Catalan Health System, through the Catalan Institute of Health (ICS), representing a successful example of how the public and private sectors can work closely together for the benefit of science, patients and society.

As an active member of the CERCA Institute of Research Centers of Catalonia (Institució CERCA–Centres de Recerca de Catalunya), this collaboration affords us access to the Catalan Research System and the fiscal and legal benefits that this represents. The financial support it has provided has consequently contributed majorly to VHIO’s structural overheads, allowing us to center our efforts on our core research activities. Additionally, our groups also receive funding from various calls promoted and supported by the Generalitat de Catalunya.

In 2021, the Government of Catalonia’s Department of Health awarded three new VHIO projects. Research led by Alena Gros, Principal Investigator of our Tumor Immunology & Immunotherapy Group, will focus on the development of personalized, non-invasive cell therapies targeting the cancer mutanome of metastatic endometrial cancer. Raquel Perez-Lopez, Principal Investigator of VHIO’s Radiomics Group, will apply precision imaging and artificial intelligence to better characterize patients’ response to cancer immunotherapy. Violeta Serra, Principal Investigator of our Experimental Therapeutics Group, will lead research to seek out predictive biomarkers of response to PARP inhibitors (PARPi) and platinum-based chemotherapy in hereditary breast and ovarian cancer.

It is thanks to one of our private patrons, the Fundació Privada CELLEX (CELLEX Foundation), that we have been able to build new facilities that have subsequently spurred our efforts aimed at advancing precision oncology and providing optimal patient treatment and care.

As a first example, it is thanks to this Foundation that the Vall d’Hebron University Hospital’s Oncology Department’s Oncology Day Hospital and Outpatients Facility opened its adjoining doors in 2008, with a subsequent and final phase of reforms in 2012. This carefully planned expansion and integration of various units and services, resulted in uniting all specialties and disciplines involved in the treatment and care of our patients in the same place and in so doing, helps to spur purely translational and multidisciplinary research for which VHIO is famed.

The CELLEX Center: the home, heart and hub of translational & transformative research at VHIO.

CELLEX also financed the construction and infrastructures of our state-of-the-art building – the CELLEX Center – that was completed back in 2015. Marking a new VHIO chapter, our premises provided the necessary space and amenities to expand our research activities and further foster our multidisciplinary connectivity and exchange by bringing all VHIO research teams together under the same roof.

Providing out teams with the valuable space through which to grow, the CELLEX Center has not only further enhanced collaborations and accelerated our dedicated efforts to combat cancer, it has also allowed us to strengthen our teams, pursue and develop new emerging research areas, and fortify our research structure.

As importantly, thanks to CELLEX, our cutting-edge Animal Facility that we share with other colleagues across the Vall d'Hebron Barcelona Hospital Campus, enables our investigators to further develop and finely-tune our predictive cancer models. Incorporating the latest platforms and technologies, this facility has helped to establish VHIO as a reference in cancer modelling.

Support received from the Fundación FERO (FERO Foundation), has, from the very outset, enabled science of excellence at VHIO as well as promoted the careers of up-and-coming talents in oncology through its annual grants and fellowships.

Concerning the former, the labs of Josep Villanueva, PI of our Tumor Biomarkers Group, Laura Soucek, PI of VHIO’s Mouse Models of Cancer Therapies Group and ICREA Research Professor, Violeta Serra, PI of VHIO’s Experimental Therapeutics Group, Joaquín Arribas, PI of our Growth Factors Group, also an ICREA Research Professor, Sandra Peiró, PI of our Chromatin Dynamics Group, and most recently, César Serrano, PI of our Sarcoma and Translational Research Group, have been able to grow their groups and advance their pioneering research lines thanks to FERO.

FERO has also contributed to the expansion of our facilities. As an example, the Foundation was a sponsor of our Breast Cancer Center Endavant i de Cara, along with a personal donation received from Maria Angels Sanahuja. Funding received from FERO also enables us to continue to develop the liquid biopsy of cancer and thus advance research into the more effective and less invasive tracking of disease. These investigations, spearhead by VHIO’s Director, Josep Tabernero, are carried out within the scope of FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV), that fuels VHIO’s Molecular Prescreening Program.

Regarding its Annual Awards for Translational Research in Oncology, a total of fourteen of our research scientists have been prized to date: Laura Soucek (2011), Héctor G. Palmer (2012), Ibrahim Yasir – formerly an investigator of VHIO’s Experimental Therapeutics Group directed by Violeta Serra (2013), César Serrano (2015), Beatriz Morancho (2016), María Abad (2017), Alena Gros (2018), Joaquin Mateo, Violeta Serra and Judith Balmaña through the first FERO-ghd funded project (2019), Raquel Perez-López, Cristina Saura and Miriam Sansó – the second annual FERO-ghd award (2020), and Nicolás Herranz in 2021.

Specifically, Nicolas Herranz, Senior Investigator of our Prostate Cancer Translational Research directed by Joaquin Mateo, was awarded this year for his project entitled, Exploiting therapy-induced senescence in a synthetic lethal approach to treat advanced prostate cancer. This funding will enable him to seek out new therapies or drug combinations that neutralize senescent cells and prevent cancer resistance in prostate cancer. This FERO Grant is supported by the Ramón Areces Foundation.

In 2021, the FERO Foundation supported an additional two new VHIO projects. Our Director, Josep Tabernero, was awarded to explore new technologies for the identification of novel biomarkers of sensitivity and resistance to targeted therapies in metastatic colorectal cancer. This research will be carried out by our Gastrointestinal & Endocrine Tumors Group, led by Teresa Macarulla. VHIO’s Joan Seoane, Principal Investigator of our Gene Expression & Cancer Group, has received FERO funding to further pursue his research into cerebrospinal fluid as liquid biopsy for the detection, characterization and treatment of brain cancer recurrence. Joan and his team have been awarded for their studies analyzing circulating DNA in the cerebrospinal fluid of pediatric patients with medulloblastoma.

Thanks to the support received from the ”la Caixa” Foundation, VHIO’s Research Unit for Molecular Therapies of Cancer (UITM) – CaixaResearch, opened its doors in 2010 to pioneer early drug discovery and clinical studies tailored to the specificities of patients. Research at this Unit has contributed to the development of several tumor cell targeted agents including trastuzumab, pertuzumab, cetuximab, panitumumab, ramucirumab, trifluridine/tipiracil, gefitinib, osimertinib, ceritinib, crizotinib, loratinib and everolimus, among others. Current focus also centers on accelerating and advancing immunotherapies including atezolizumab, nivolumab and pembrolizumab.

The UITM, under the direction of Elena Garralda, Principal Investigator of our Early Clinical Drug Development Group, has subsequently established itself as a leading reference in developing novel therapies based on the molecular profile of each tumor and optimizing treatment strategies using combinations of new agents with already existing ones. It also pioneers the design and development of novel, adaptive clinical studies including the basket, multi-modular and umbrella trials. Elena’s team is dedicated to studying the efficacy of treatment approaches and anti-cancer medicines by allowing for the ‘real time’ and necessary adaptation in tune with the rapid pace of cancer discovery - especially in the academic setting.

By advancing clinical trial study design in the current era of precision medicine, VHIO continues to make important contributions to tackling the current challenges in oncology including the globalization of clinical research, and the implementation of emerging health technologies in the clinical setting. One major development in these directions, was the launch of the EU-funded, multi-site project, Cancer Core Europe Building Data Rich Clinical Trials - CCE-DART, which is coordinated by Elena Garralda.

In addition to various grants supporting several VHIO groups and projects, the Foundation also fuels one of VHIO’s three major institutional programs. Building on the successes of the two previous VHIO – ”la Caixa” Institutional 3-year Programs, at the beginning of 2020, we launched a new 4-year VHIO – ”la Caixa” program: CaixaResearch Advanced Oncology Research Program, 2020-2023. This support further spurs our purely translational and multidisciplinary teams to develop more potent and precise anti-cancer medicines, fortify existing research lines as well as initiate new projects to lead frontier research in some of the most relevant and emerging focus fields in precision oncology.

It is also thanks to the ”la Caixa” Foundation that VHIO’s Clinical Research Oncology Pharmacy Unit’s new home was completed in 2019. Providing the much-needed additional space and equipped with the very latest technologies, the Molecular Therapy of Cancer (UITM) – CaixaResearch Clinical Research Onco-Hematology Unit enables Isabel Cidoncha’s team to provide even higher quality pharmaceutical care and services, as well as continue to meet all the regulatory requirements.

Four new VHIO projects received funding from the ”la Caixa” Foundation in 2021. First, thanks to an awarded Health Research ”la Caixa” Project, Elena Élez, Medical Oncologist and Clinical Investigator of our Gastrointestinal & Endocrine Tumors Group, will lead the PROMISE study: BioPrinted hydROgel MicrofluIdicS to mimic patient-specific tumor mEtastatic.

Under the scope of the ”la Caixa” InPhinit Retaining and InPhinit InComing funding programs, a trio of predoctoral projects have been granted. Concerning the former, Olivia Prior, a PhD student of our Radiomics Group, will aim to decipher spatial and temporal cancer heterogeneity with machine learning and precision imaging, under the mentorship of Principal Investigator Raquel Perez-Lopez.

Mentored by Maria Abad, Principal Investigator of VHIO’s Cellular Plasticity & Cancer Group, a Graduate Student of her group, Marion Martínez will carry out her research project entitled, OncoPeptides: mining the secreted microproteome for novel regulators of PDAC biology. The IPhinit InComing ”la Caixa” Foundation fellowship, will support Ariadna Grinyó, a Graduate PhD Student of Joaquín Arribas’ Growth Factors Group. Supervised by Joaquín, her research project centers on armoring a p95HER2 CAR T for the controlled secretion of antitumor agents upon T-cell activation.

Finally, through our VHIO – CaixaResearch Scientific Seminars Series, launched in 2019, we continue to welcome internationally renowned researchers and clinical investigators to VHIO to share, discuss and debate latest insights, discovery and next directions in oncology with our students, postdocs and senior faculty from our preclinical, translational and clinical research groups. Naturally, due to the COVID-19 pandemic, these expert sessions were mostly hosted and conducted virtually. In 2021, a total of 23 VHIO - CaixaResearch Scientific Seminars took place.

Driving programs to spur VHIO’s avant-garde translational research in precision oncology, the Fundación BBVA (BBVA Foundation), financed our Tumor Biomarkers Research Program back in 2011. This five-year major framework agreement fueled collaborative science centering on the development of personalized therapies for cancer patients through biomarker research. Building on the successes of this very first program, our second BBVA-VHIO Institutional Program: the BBVA Comprehensive Program of Cancer Immunotherapy & Immunology - CAIMI, represents an important forward step in advancing agents that inhibit checkpoint regulation of the immune system, better understanding mechanisms of resistance and response to these therapies, and prioritizing the early development of those drugs showing most promise. It also supports various research lines across other VHIO groups. Under the leadership of VHIO’s Director, Josep Tabernero, these research efforts are headed by Alena Gros and Elena Garralda, Principal Investigators of our Tumor Immunology & Immunotherapy and Early Clinical Drug Development Groups, respectively, in collaboration with VHIO’s in-house Molecular Prescreening Program of excellence, (please also see: FERO Foundation’s Advanced Molecular Diagnostics Program – DIAMAV). Main objectives of the BBVA Foundation’s CIAMI program include achieving a deeper understanding of naturally occurring T-cell response to cancer and establishing novel ways to exploit these anticancer responses to develop more effective, powerful and personalized immune-based strategies, approaches and therapies to combat this disease; across several tumor types. Various pioneering translational projects linked to the early clinical development phases of immunotherapy are underway. Focus areas include the characterization of hyperprogressive disease with immunotherapy to advance insights into this phenomenon, led by Elena Garralda, Principal Investigator of VHIO’s Early Clinical Drug Development Group. Carried out in collaboration with Raquel Perez-Lopez, PI of our Radiomics Group, a radiomic signature has been developed to more precisely predict response to immunotherapy. Importantly, thanks to the funding received through CAIMI, Elena Garralda’s team and Alena Gros’ group have worked together to finalize the clinical grade validations of tumor-infiltrating lymphocytes (TILs) expansion for the treatment of certain cancer patients at the Vall d’Hebron University Hospital (HUVH). This work was carried out in collaboration with the Banc de Sang i Teixits - BST (Blood and Tissue Bank), a public agency of the Catalan Department of Health. Alena's group, together with Elena Garralda's team, has received authorization from the AEMPS, and initiated patient recruitment for a phase I clinical study to test the safety and tolerability of neoantigen-selected TIL for patients with solid tumors refractory to standard therapies.

VHIO's TRANSLATION TOWARD PRECISION ONCOLOGY: A LITTLE MORE ON HOW WE DID IT IN 2021

Located within the Vall d’Hebron Barcelona Hospital Campus, our researchers and clinical investigators work together as multidisciplinary teams. Also incorporating physician-scientists and other professionals as well as disciplines in oncology at our Vall d’Hebron University Hospital (HUVH), translational science and clinical research are therefore tightly connected which promotes superb interaction and teamwork which, in turn, accelerates the bench to bedside and back cycle of knowledge.

This privileged environment affords VHIO direct access to patients as well as the entire spectrum of oncology professionals who care for them, and a second-to-none appreciation of how cancer science can translate into more powerful, targeted treatments and better practice for the care of patients.

VHIO’s transformative model, coupled with its belief in combining strengths through cross-border collaborations, continue to spur advances in reversing cancer resistance, halting metastatic spread, and more effectively treating even the most ‘undruggable’ tumor types.

VHIO’s multidisciplinary and translational model: the seamless, unrestricted Flow of discovery in oncology.

Areas of cancer research at VHIO: a snapshot

  • Preclinical humanized models (PDXs – Avatars – and Organoids).
  • Mechanisms of sensitivity, and primary and acquired resistance.
  • Molecular and clinical Big Data to characterize subtypes of disease.
  • Early drug development.
  • Clinical trials with innovative agents (phase I & II) and first-in-human studies.

Advancing translational and transformative clinical research against cancer

The Fundació Privada CELLEX (CELLEX Foundation), one of VHIO’s Patrons and Institutional Supporters, financed the construction of our state-of-the-art building – the CELLEX CENTER – that was completed back in 2015. Also supporting our infrastructures, the CELLEX Foundation enables us to advance translational cancer science through our purely multidisciplinary research model and interconnected facilities and platforms.

In 2021, 446 scientific articles were published by VHIO researchers as corresponding/senior or co-authors. For a selection of some of the most relevant articles by VHIO researchers published this year please click here.

To view each Principal Investigator’s Paper Pick 2021 (highlighting a maximum of four selected contributions in 2021), please refer to their corresponding group.

COVID-19 pandemic papers

Like many other biomedical research institutes in 2021, VHIO researchers also joined the historic, scientific effort in the COVID-19 era by (co) leading essential research into the impact of this virus on cancer patients as well as professionals in oncology.

Just some of our contributions included the following:
Presented at the virtual 2021 Annual Congress of the European Society for Medical Oncology (ESMO), updated analysis of the OnCOVID registry, directed by David J. Pinato, Imperial College London (UK), and co-authored by Juan Aguilar-Company, Internal Medicine & Infectious Diseases specialist at the Vall d’Hebron University Hospital’s (HUVH) Medical Oncology Department, headed by Josep Tabernero, who also co-authored this study, evaluated the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer in Europe.

For this retrospective study, over 2,700 patients were enrolled from 35 centers who were diagnosed with SARS-CoV-infection between February 2020 – February 2021. Analysis focused on COVID-19 survivors who underwent clinical reassessment at each participating institution, including HUVH. The investigators documented the prevalence of COVID-19 sequelae and described factors implicated in their development and their association with post-COVID-19 survival, defined as the interval resumption of systemic anti-cancer medicines in patients treated within 4 weeks of a COVID-19 diagnosis.

Based on the data from over 1,500 patients who survived COVID-19, results from this study (1) show that sequelae post-COVID-19 compromise long-term survival and outcomes, affecting up to 15% of patients with cancer after recovery. The OnCovid study investigators concluded that adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients.


Also presented during ESMO 2021, results from a study led by clinical researchers at VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, directed by Elena Garralda, reported on the impact of the COVID-19 pandemic on Phase I studies at our Institute.

Presented by Maria Julia Lostes Bardaji, a phase I Investigator at our UITM-Caixa Research, and Silvia Perez-Pujol, Head of VHIO’s Start Up Unit, while data showed an initial decrease in new clinical studies during 2020, digitalization and measures in place proved effective in maintaining activity; leading to an increase in the number of new proposals for phase I studies at the end of 2020 at this Unit. The investigators also observed a more significant increase in proposals from January to July 2021.

The researchers analyzed statistics relating to the initiation of phase I clinical trials from January 2019 to July 2021, including new study proposals, pre-selection and study initiation visits. Data showed that while there was a 9.6% decrease in new clinical trial proposals in 2020 compared with 2019, dropping from 146 to 132, the number of pre-selection as well as initiation site visits increased in 2020.

The investigators concluded that, despite the challenges posed by COVID19 and the subsequent, initial decrease of new studies observed during 2020, their findings demonstrated that the number of new proposals for phase I clinical trials increased in 2021. This trend supports the efficiency of remote pre-selection site visits as an alternative to on-site visits, and the efficacy of digitalization and measures in place to maintain clinical start up activity at VHIO during the pandemic.


Led by Elena Élez, a Medical Oncologist and Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group, a study (2) conducted on behalf of the Spanish Society of Medical Oncology (SEOM) and the +MIR SEOM Residents and Young Oncologists Committee, assessed the prevalence of burnout in junior medical oncologists in Spain - before and after the onset of the COVID-19 pandemic.

The investigators, including first author Pablo Jiménez Labaig, Member of +MIR SEOM and a Medical Oncologist at the Cruces University Hospital, Barakaldo (Bizkaia, Spain), conducted two online surveys aimed at residents and medical oncologists in their first five years post-residency.

Findings showed that almost one out of four young oncologists surveyed had doubts concerning their medical vocation. Results from the first survey revealed that 28% of respondents were affected by burnout, increasing to almost 36% in residents in their second year of training. It also identified other issues that can lead to professional exhaustion including the perceived lack of vacation and leisure time and struggle to strike a better work-life balance.

Almost 84% of survey participants confirmed that they had missed part of their training rotations and medical stays at other hospitals in Spain and abroad. Nearly three-quarters of respondents were reassigned to COVID-19 care in challenging work conditions, and 17% of them reported that they had contracted COVID-19.

Regarding mental health, 37% had scores indicating anxiety, 30% with moderate to severe depression, and 64% of survey participants confirmed that they had no access to psychological support at the workplace. These worrisome findings raise an alarm concerning the lack of measures aimed at reducing burnout suffered by many of our younger medical oncologists.

VHIO’s Elena Élez coordinates the +MIR SEOM Residents and Young Oncologists Committee. Her devotion to nurturing and growing the careers of young investigators and medical oncologists is also reflected by her co-leadership of VHIO’s recently established Academy.


(1) Pinato DJ, Tabernero J, Bower M, Scotti L, Patel M, Colomba E, Dolly S, Loizidou A, Chester J, Mukherjee U, Zambelli A, Dalla Pria A, Aguilar-Company J, Ottaviani D, Chowdhury A, Merry E, Salazar R, Bertuzzi A, Brunet J, Lambertini M, Tagliamento M, Pous A, Sita-Lumsden A, Srikandarajah K, Colomba J, Pommeret F, Seguí E, Generali D, Grisanti S, Pedrazzoli P, Rizzo G, Libertini M, Moss C, Evans JS, Russell B, Harbeck N, Vincenzi B, Biello F, Bertulli R, Liñan R, Rossi S, Carmona-García MC, Tondini C, Fox L, Baggi A, Fotia V, Parisi A, Porzio G, Saponara M, Cruz CA, García-Illescas D, Felip E, Roqué Lloveras A, Sharkey R, Roldán E, Reyes R, Earnshaw I, Ferrante D, Marco-Hernández J, Ruiz-Camps I, Gaidano G, Patriarca A, Bruna R, Sureda A, Martinez-Vila C, Sanchez de Torre A, Cantini L, Filetti M, Rimassa L, Chiudinelli L, Franchi M, Krengli M, Santoro A, Prat A, Van Hemelrijck M, Diamantis N, Newsom-Davis T, Gennari A, Cortellini A; OnCovid study group. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study. Lancet Oncol. 2021 Dec;22(12):1669-1680.
(2) Jiménez-Labaig P, Pacheco-Barcia V, Cebrià A, Gálvez F, Obispo B, Páez D, Quílez A, Quintanar T, Ramchandani A, Remon J, Rogado J, Sánchez DA, Sánchez-Cánovas M, Sanz-García E, Sesma A, Tarazona N, Cotés A, González E, Bosch-Barrera J, Fernández A, Felip E, Vera R, Rodríguez-Lescure Á, Élez E. Identifying and preventing burnout in young oncologists, an overwhelming challenge in the COVID-19 era: a study of the Spanish Society of Medical Oncology (SEOM). ESMO Open. 2021 Aug;6(4):100215.


The development and application of powerful platforms & empowering technologies

At the core of VHIO’s research activities are our suite of cutting-edge core technology platforms which allow our expert teams to apply next-generation whole-genome sequencing for precision oncology as well as develop and improve existing applications to accelerate results.

By sequencing panels of genes or entire genomes in cancer patients, we are now better equipped than ever before to identify specific molecular risk factors and better predict the potential efficacy of specific agents matched to the specificities of individual patients.

VHIO’s Cancer Genomics Group, headed by Ana Vivancos, serves as a Core Technology laboratory and provides cutting-edge applications in cancer genomics through state-of-the-art technologies and the development of novel, fully validated tests that are used in the clinical research setting. Her lab is equipped with an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and four NextGen Sequencers; MiSeq, NextSeq and HiSeq2500 from Illumina, and most recently, a MinION from Oxford Nanopore Technologies.

At the preclinical and translational level, VHIO was the first academic test center to incorporate in-house BEAMING liquid biopsy RAS biomarker technology (2015). As highlighted throughout the pages of this scientific report, thanks to our multidisciplinary teams in collaboration with VHIO’s Cancer Genomics Group and Paolo Nuciforo’s Molecular Oncology Group we continue to make significant progress in validating and developing liquid biopsy technologies for the more effective, less invasive monitoring of cancer in real time.

In 2021, we incorporated Guardant Health liquid biopsy. As the first cancer research center to do so in Europe, this avant-garde platform provides complete genomic results in all solid tumors from a simple blood test in seven days and will therefore help to overcome the limitations associated with traditional tissue biopsy. Guardant360 CDx technology -- the first liquid biopsy test for comprehensive genomic profiling to have received approval from the U.S. Food and Drug Administration (FDA) – will facilitate the non-invasive detection of an increasing number of mutations for the more precise selection of therapies matched to the molecular specificities of each individual patient’s disease.

Integrating this new technology into VHIO’s expanding suite of cutting-edge platforms will further accelerate progress in developing and advancing next generation therapies and precise diagnostics in precision oncology. Also in liquid biopsy, Ana’s group has developed their custom NGS test with Unique Molecular Identifiers (UMIs) combined with Copy Number Alteration analysis using Shallow Whole Genome Sequencing (sWGS), that will be their first disease tracking test in the clinical setting.

Molecular Prescreening at VHIO: driving the clinical implementation of emerging cancer biomarkers

VHIO’s Molecular Prescreening team (left to right): Ana Vivancos, Elena Garralda, Paolo Nuciforo, Rodrigo Dienstmann, Susana Aguilar and Jenifer González.

VHIO's Molecular Prescreening Program is powered by one of our Institutional Programs, FERO Foundation’s Institutional Advanced Molecular Diagnostics Program – DIAMAV, and catalyzes precision medicine at VHIO. Over the past decade, molecular prescreening at VHIO has provided access to advanced molecular diagnostics to an increasing number of patients, and is critical in matching targeted therapeutic approaches with hundreds of clinical trial opportunities.

Molecular prescreening at VHIO also counts on the expertise provided through our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, funded by the ”la Caixa” Foundation and directed by Elena Garralda. Representing a key driver of clinical-molecular correlative research at our Institute, this program is co-led by VHIO’s Ana Vivancos, Elena Garralda, Paolo Nuciforo, and Rodrigo Dienstmann. The team regularly convenes to explore existing molecular tests, developed in-house, and novel biomarkers of interest for the potential inclusion in the program.

Performing molecular profiling in over 1,100 patients each year, VHIO is one of the few centers in Europe to run such a comprehensive program.

In 2021, tumor molecular profiling was performed in 1,138 cancer patients who are candidates for enrolment in clinical studies. Our cancer researchers and genomicists participate in weekly tumor board meetings with VHIO’s medical oncologists to provide guidance on the interpretation of NGS results as well as discuss new markers for clinical testing in patients eligible for inclusion in our early phase clinical studies performed at our UITM – CaixaResearch.

Further developments this year also include the validation of our Cancer Genomics Group’s 450 gene capture panel for mutations, Tumor Mutational Burden and for Copy Number Alterations, to be used in our molecular prescreening, and research led by Paolo Nuciforo, Principal Investigator of VHIO’s Molecular Oncology Group, continues to identify targetable alterations as part of this program.

Flanking these efforts, our VHIOTECA Unit was created in 2021 to support investigators for the obtention, registration and preservation of biological samples other than tumoral tissue (plasma, feces, saliva) from cancer patients, and facilitate the use of these samples in research projects. Joining our other transversal clinical trials core services, VHIOTECA’s team is headed by Susana Aguilar, who also coordinates our Molecular Prescreening Program in collaboration with Jenifer González, Research Support Technician of our Cancer Genomics Group.

We continue to extend our efforts to an increasing number of patients through collaborations with other research centers, across borders. As an example, VHIO participates in the AACR’s Genomics Evidence Neoplasia Information Exchange project (GENIE) that catalyzes the sharing of integrated genomic and clinical datasets across multiple cancer centers worldwide. Incorporating 20 consortium participants across the globe, VHIO is the only institution from Spain. This major international collaboration also counts on the expertise of its informatics partners, SAGE and cBioPortal, that serve as secure data repository and visualization portals. The first set of cancer genomic data aggregated through AACR’s GENIE was available to the global oncology community in January 2017. The ninth data set, GENIE 9.0-public, was released in February 2021, and the tenth, GENIE10.0 public, followed in June 2021. Most recently, this project has hit another important milestone. With the release of GENIE 11.0-public, the registry now contains over 136,000 sequenced samples from over 121,000 patients, making the AACR Project GENIE registry among the largest fully public cancer genomic data sets released to date. Fulfilling an unmet need by providing the necessary statistical power to better guide clinical decision-making, particularly in the case of rare cancers and rare variants in common cancers, GENIE empowers novel clinical and translational research. VHIO was invited to join this pioneering project in 2018 and our participation is led by Rodrigo Dienstmann, Principal Investigator of our Oncology Data Science (ODysSey) Group.


VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch: spearheading early clinical drug development and dynamic studies in precision oncology

VHIO’s UITM - CaixaResearch: the heart and hub of our early clinical drug development.

Thanks to the support we receive from one of our Institutional Supporters and Patrons, ”la Caixa” Foundation, VHIO continues to establish itself as a leading reference in progressing drug development and targeted therapies against cancer. Our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, founded back in 2010, has rapidly become one of the few comprehensive facilities in Europe to translate latest discovery into improved outcomes for patients, as rapidly as possible.

Directed by Elena Garralda, alongside our Director, Josep Tabernero, it has been able to do so not only through the bridging and tight connectivity between health care professionals, VHIO researchers and clinical investigators, but also by identifying novel predictive markers of response to anti-cancer therapies and markers of primary resistance (de novo) and secondary treatment.

Research at this Unit is driven by Elena Garralda’s Early Clinical Drug Development Group, and focuses on the development of novel agents based on the molecular profile of each tumor as well as the optimization of therapies using combinations of new drugs with existing ones. These efforts have contributed to the development of several tumor cell targeted agents including trastuzumab, pertuzumab, cetuximab, panitumumab, ramucirumab, trifluridine/tipiracil, gefitinib, osimertinib, ceritinib, crizotinib, loratinib and everolimus, among others.

As a direct result of clinical studies conducted at our UITM-CaixaResearch, more than 30 anti-cancer agents by either the U.S. Food and Drug Administration (FDA), or the European Medicines Agency (EMA), or both.

Current research centers on accelerating and advancing immunotherapies including atezolizumab, nivolumab and pembrolizumab. Concerning novel immunotherapeutics, we spearhead the early drug development of these agents and cell signaling. Specifically, we focus on second generation immunotherapies, including new cytokines, bispecifics, intratumoral agents, immunomodulatory agents and immune checkpoint inhibitors and combinations, as well as translational research in immuno-oncology in collaboration with several VHIO groups, including Alena Gros’ Tumor Immunology & Immunotherapy Group.

Pioneering next generation, adaptive clinical studies

Our UITM-CaixaResearch facilities, coupled with VHIO’s CaixaResearch Advanced Oncology Research Program, 2020-2023, enable us to continuously expand our portfolio of early phase studies including complex trials such as basket studies, as well as spearhead next generation clinical trials in oncology.

Our participation in ongoing and new projects including the EU-funded Cancer Core Europe Consortium – Building Data Rich Clinical Trials (CCE-DART), that officially launched in 2021, also allows us to optimize biomarker-drug co-development to more precisely match tailored therapies to each disease setting, each individual patient. These ‘smarter’ study designs seek to more effectively identify the optimal treatment for the right patient, at the right time. They also promise to overcome the rigidity and limitations of traditional clinical trials.

Throughout 2021, despite the challenges posed by the COVID-19 pandemic, our Unit led 207 ongoing phase I plus Basket clinical trials – an increase over previous years. Similarly, more patients than ever before were enrolled in our phase I and basket studies. This year, 551 patients participated in these studies. It is thanks to the dedication of Elena Garrlda’s Group, and all our expert professionals across VHIO’s Transversal Clinical Trials Core Services and Units, that activity was successfully maintained, and in some instances even surpassed, in order to respond to the needs of our patients.


VHIO’s Clinical Trials Office, directed by Marta Beltran, is also located in the patient environment of the Vall d’Hebron University Hospital (HUVH). Her team coordinates our phase I and Basket studies, and a large portfolio of phase II & III clinical trials. In 2021 a record total number of 1,326 patients were enrolled across our 511 actively recruiting trials. In addition, 280 patients were included in a total of 34 post authorization and rollover studies.

Overall, this increased activity was largely achieved by establishing adaptive circuits and approaches to ensure the optimal running of clinical studies, while delivering –as always- optimal patient care. Newly introduced measures in response to the pandemic, whenever and wherever possible, included remote monitoring as well as dispensation of medication for certain patients receiving orally administered therapies, and telematics clinical consultations. Additionally, the virtual monitoring of certain patients in clinical trials quickly emerged as a solution to some issues posed by COVID-19.


VHIO's direct access to cancer patients: at the center of our purely translational research model

The Vall d'Hebron University Hospital (HUVH): the largest hospital complex in Catalonia and one of the most important in Spain.

Located within the Vall d’Hebron Barcelona Hospital Campus, which also incorporates a trio of research institutes of international reference; Vall d’Hebron Institute of Research (VHIR), CEMCAT – Multiple Sclerosis Center of Catalonia, and VHIO, the Vall d’Hebron University Hospital (HUVH), affords VHIO direct access to patients as well as the entire spectrum of oncology professionals who care for them.

Organized into multidisciplinary and integrated teams, our researchers closely collaborate and interact with Vall d’Hebron physician-scientists. Translational science and clinical research are therefore tightly connected, accelerating the bench-bedside-bed cycle of knowledge.


VHIO’s trio of institutional programs: delivering on the promise of precision medicine and potentiating novel therapies and treatment strategies

VHIO can only continue to accelerate the pace in advancing personalized and targeted therapies against cancer thanks to the generous support received from our Patrons and Institutional Supporters: the Generalitat de Catalunya, Fundació Privada CELLEX, Fundación FERO, ”la Caixa” Foundation, and the Fundación BBVA. In addition to this precious funding, three of them also fuel our trio of Institutional Research Programs:

Advanced Molecular Diagnostics Program – DIAMAV. This program supports molecular prescreening at VHIO as we seek to advance molecular profiling in patients to more effectively match personalized treatment strategies based on the genomic or pathologic profile of each individual patient and the molecular makeup of their disease. Our investigators aim to identify specific molecular risk factors to better predict the potential efficacy of specific agents tailored to each particular tumor, advance insights into the more precise and less invasive tracking of disease by liquid biopsy, and develop cancer diagnostics for the early detection of disease.

CaixaResearch Advanced Oncology Research Program. Building on the successes of the two previous VHIO – ”la Caixa” institutional 3-year programs, our CaixaResearch program - 2020-2023, enables our researchers and investigators to accelerate the development of more potent and targeted anti-cancer medicines, strengthen existing research lines as well as initiate new projects to lead frontier research in some of the most relevant and rising focus fields in precision oncology; those areas showing particular promise in solving the multiple questions that stand in the way of more effectively combating cancer.

Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI). As a result of the achievements of the very first VHIO – BBVA Foundation Program on Tumor Biomarkers Research, the BBVA Foundation officially launched this second 4-year program in 2018 to advance agents that inhibit checkpoint regulation of the immune system, achieve a deeper understanding of mechanisms of resistance and response to these therapies, and prioritize the early development of those agents showing most promise.


Our research efforts and activities are also supported by funding received from several private institutions, companies, associations, societies, and individual donors. In addition, we continue to secure essential funding through several International and National Competitive Grants. Regarding the latter, we take this opportunity to also gratefully thank the Asociación Española Contra el Cáncer – AECC (Spanish Association against Cancer) for its longstanding support of several VHIO groups and researchers.


Powerful cross border partnerships of excellence

At VHIO we are dedicated to fostering, developing and (co) leading multi-center collaborations that combine the necessary expertise and resources to more rapidly advance cancer discovery. Regarding our leadership of -and participation in- several existing international consortia and alliances, 2021 marked many important developments including the following:

The Cancer Core Europe Consortium – CCE, promotes the pooling and exchange of expertise, research findings, common platforms and processes, and empowers researchers and clinicians to rapidly exploit this trove of biological insights and clinical data for the benefit of patients. It also spearheads next generation clinical trials by designing and developing data rich, dynamic studies in oncology.

Officially announced in 2021, multi-site EU Horizon 2020-funded Cancer Core Europe Consortium-Building Data Rich Clinical Trials (CCE-DART) incorporates experts from the seven European comprehensive cancer centers belonging to the CCE Consortium, including VHIO, along with an additional four non-CCE partners*. Led by VHIO’s Elena Garralda, Principal Investigator of our Early Clinical Drug Development Group), and Director of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, this project is Illustrative of our collaborative efforts aimed at pioneering novel clinical trial design in the current era of precision oncology.

Building on the CCE-developed Basket of Baskets (BoB) investigator-initiated and adaptive trial which launched in 2018, which was also designed and co-developed by Elena’s team at UITM-CaixaResearch, CCE-DART will further enhance BoB’s harmonized, molecular multi-tier profiling platform to more precisely match patients to novel anti-cancer medicines based on the genetic specificities of their individual tumors. In parallel, the researchers will continue to develop multiple treatments in genomically-selected populations.

By harnessing and incorporating powerful cutting-edge technologies, methods and platforms, CCE-DART investigators will spur the design, development, and ringing in of a new generation of data rich, dynamic studies in oncology. To overcome the rigidity and limitations of traditional randomized controlled trials that do not allow for the ‘real time’ and necessary adaptation in tune with the rapid pace of cancer discovery – especially in the academic setting, these novel clinical studies promote the optimization of biomarker-drug co-development toward more precisely tailoring therapies to each disease setting, each individual patient.

Common infrastructures and the wealth of experience gained through CCE sites’ running of innovative academic studies will help the project partners to deliver on the four key objectives. Namely, to improve patient enrolment strategies and trial designs, accelerate the use of novel health technologies in the clinical setting, optimize clinical trial data management and analysis, and globalize the results of the project by promoting transparency of investigator-initiated studies.

www.cce-dart.com

This project has received funding from the European Union’s Horizon 2020 framework programme research under grant agreement No. 965397.

*CCE-DART participants - CCE Consortium Members: VHIO, Karolinska Institute, (Stockholm, Sweden), Cambridge Cancer Center (Cambridge, UK), National Center for Tumor Diseases (Heidelberg, Germany), Netherlands Cancer Institute, (Amsterdam, The Netherlands), National Cancer Institute of Milan (Italy). Gustave Roussy Cancer Campus Grand Paris (Villejuif, France). Non-CCE Members: Digital Experimental Cancer Medicine Team (Manchester, UK), The Hyve (Utrecht, The Netherlands), DataRiver (Modena, Italy), Form Vision (Abcoude, The Netherlands).


Regarding the aforementioned CCE Basket of Baskets (BoB) modular, open-label, phase II, multicenter study evaluating targeted agents in molecularly selected populations with advanced solid tumors, a new iBASKET therapeutic module was introduced in 2021.

Also led by VHIO, this addition will focus on the targeting of fibroblast growth factor (FGFR) genomic alterations present in multiple tumor types. Incorporating four different arms, investigators will assess the anti-tumor activity and efficacy of FGFR inhibitor futibatinib in patients with FGFR-aberrant solid tumors.

www.basketofbaskets.eu


The European-Canadian Cancer Network (EUCANCan) Consortium launched in 2019 to pursue the homogeneous analysis, management and exchange of genomic-driven oncology data for the advancement of precision medicine against cancer.

This four-year project, coordinated by David Torrents, ICREA Professor and Head of Computational Genomics at the Barcelona Supercomputing Center (Spain), is jointly fueled by the European Union’s Horizon 2020 research and innovation programme and the Canadian Institutes of Health Research (CIHR).

As a federated network comprising interoperable infrastructures in Canada, Germany, the Netherlands, France, and Spain, leading experts in oncogenomics and cancer data science from 18 organizations, including VHIO’s Rodrigo Dienstmann (PI: Oncology Data Science – ODysSey), swiftly apply and exchange genomic-generated intelligence and discovery.

VHIO’s participation, also counting on the expertise of our Director, Josep Tabernero, and Elena Garralda (Director, UITM-CaixaResearch) focuses on standardizing clinical-genomics datasets for precision oncology and creating webtools that will expand patient access to biomarker-driven trials in Europe. These efforts (Work Package 5: Standardized clinical reporting across sites), are co-directed by Rodrigo Dienstmann and Jürgen Eils, Heidelberg University Hospital (UKL) – German Cancer Research Center (DKFZ).

www.eucancan.com

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 825835.


As part of the EUCANCan project, VHIO’s Onco Trials Track launched in 2021. Designed and developed by Rodrigo Dienstmann’s team, this online resource empowers healthcare providers in the difficult and time-consuming task of finding the most suitable VHIO clinical trial for cancer patients and contacting investigators from recruiting sites for case discussion and referral.

Unlike many other available databases, Onco Trials Track offers a user-friendly interface with up-to-date catalogue of molecularly and semantically tagged clinical trials. This interactive VHIO clinical trial locator provides the very latest information on clinical trial recruitment and enables the easy identification of clinical studies with unique biomarker criteria for precision cancer therapy.

Clinical studies can be filtered by tumor type, disease stage, investigational drug class phase of clinical development, among other indicators. This VHIO-developed hub also promotes the possible acceleration of patient referral processes by completing detailed contact e-forms. Discover more here:

www.oncotrialstrack.vhio.net


Funded by the European Union’s Horizon 2020 research and innovation programme, the NoCanTher – Nanomedicine upscaling for early clinical phases of multimodal cancer therapy – Consortium, launched in 2016, and is coordinated by IMDEA Nanociencia (Madrid, Spain). Connecting 11 leading European research centers, including VHIO, along with industry partners, this multi-center undertaking also counts on the expertise of the CIBBIM-Nanomedicine Group at the Vall d’Hebron Research Institute – VHIR (Barcelona, Spain).

NoCanTher focuses on the development of magnetic nanoparticles and magnetic hyperthermia for the intra-tumoral treatment of patients with unresectable, locally advanced pancreatic cancer that has not metastasized. Currently the only therapeutic alternative for these patients, who account for 20% of patients with pancreatic cancer, is palliative chemotherapy. This pioneering project represents an important step forward in applying nanoparticles for the more effective and direct targeting of cancer cells in this patient population.

Announced in 2021, NoCanTher has now rolled out the clinical phase of the project. The pilot trial, designed and developed by VHIO’s Teresa Macarulla, Principal Investigator of our Gastrointestinal & Endocrine Tumors Group, is underway and shows promise in ultimately ringing in nanotechnology-based therapies at the clinical level.

This study is based on the results obtained in the preclinical phase of NoCanTher co-led by VHIR’s CIBBIM-Nanomedicine Drug Delivery and Targeting Group, directed by Simo Schwartz Jr. This preclinical work verified the efficacy of nanoparticles in animal models with implanted patient-derived pancreatic tumors that were previously induced. The investigators showed that when magnetic iron oxide nanoparticles are injected directly into tumors, the generated hyperthermia achieves cancer shrinkage and alters the characteristics of tumors; facilitating the direct delivery of chemotherapy.

This strategy, now being put to the test in the clinical setting, allows heat to be exclusively applied to the area where the nanoparticles are located without harming the surrounding healthy tissues. Magnetic hyperthermia, together with the administration of standard chemotherapy, can transform electromagnetic energy into heat in order to destroy tumor cells and locally control cancer growth. The intracellular delivery also promises to reduce the adverse effects associated with chemotherapy.

Marking the final phase of the NoCanTher project, this clinical study could ultimately open new therapeutic avenues for patients with locally advanced pancreatic cancer, for whom there are no other treatment options available except chemotherapy.

www.nocanther-project.eu www.cce-dart.com

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 685795.


Launched in 2021, the PERSIST-SEQ, multi-center consortium is a five-year public-private partnership aimed at building a reproducible single-cell sequencing workflow to capture tumor drug persistence. This project aims to provide the cancer research community with a new gold standard workflow for single-cell sequencing by developing and validating best practices as well as generating and analyzing high-quality FAIR data.

Led by Principal Investigator Alexander van Oudenaarden, Hubrecht Institute (Utrecht, The Netherlands), PERSIST-SEQ connects 16 partners, including VHIO, and is co-directed by the Oncode Institute (Utrecht) and AstraZeneca. Funded by the Innovative Medicines Initiative (IMI), this project represents an important step forward in developing smarter, standardized and reproducible approaches to effectively predict, target, and combat drug-resistance in cancer.

Leading experts in cancer modelling and the development of single-cell sequencing technologies will advance insights into the complexity and heterogeneous response of single-cell-derived persisters to anti-cancer therapies. Our Institute will provide clinical expertise and patients’ samples (pre, post and on-treatment), develop sophisticated mouse models linked to clinical trials, and Héctor G. Palmer, Principal Investigator of our Stem Cells & Cancer Group, will direct one of the defined work packages on single-cell acquisition from models of tumor plasticity.

This coalition comprises field-leading researchers as well as medical oncologists who will leverage their cancer modelling approaches and cutting-edge platforms to perform the sequencing of single tumour cells. Aimed at refining and standardizing a broadly applicable workflow for single-cell sequencing, PERSIST-SEQ teams will aim to advance insights into therapeutic resistance in cancer toward developing more effective therapies and prevent disease persistence.

Importantly, PERSIST-SEQ will employ an open access model to build and sustain its benchmarking procedures and centralized European data infrastructure. This strategy will help to avoid costly duplication of efforts, promote collaboration across disciplines, and facilitate the adoption of state-of-the-art single cell technologies.

www.persist-seq.org

PERSIST-SEQ receives funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 101007937.


Strengthening our programs and supporting VHIO’s research talents

As our Institute goes from strength to strength, and seeks to further develop its research lines and projects based on strategic directions, we continue to expand our scientific faculty. As highlighted in our Director’s Foreword, to this scientific report, 2021 celebrated the incorporation of two new VHIO team leaders:

Jose A. Seoane, Principal Investigator, Cancer Computational Biology Group.

Jose A. Seoane joined us to establish and lead VHIO’s Cancer Computational Biology Group which focuses on leveraging epi(genetic) cancer datasets to unmask the molecular mechanisms implicated in cancer initiation, progression, drug resistance and metastasis.

Lara Nonell, Head, Bioinformatics Unit.

Expanding our Core Technologies Program, Lara Nonell has set up VHIO’s Bioinformatics Unit to implement state-of-the-art pipelines and develop tools for the analysis and visualization of different omics datasets, including publicly available datasets.




Susana Aguilar, Head, VHIOTECA Unit.

Our VHIOTECA Unit headed by Susana Aguilar, was created in 2021 to support investigators for the obtention, registration and preservation of biological samples other than tumoral tissue (plasma, feces, saliva) from cancer patients, and facilitate the use of these samples in research projects. This Unit also compliments VHIO’s Molecular Prescreening Program, which continues to be coordinated by Susana, alongside Jenifer González, a Research Support Technician at VHIO’s Cancer Genomics Group.


Left to right: VHIO Academy Co-Chairs, Elena Élez, Clinical Investigator and Medical Oncologist, Gastrointestinal & Endocrine Tumors Group, Maria Abad, Principal Investigator, Cellular Plasticity & Cancer Group, and Clara Caminal, Head of the Academy.

Launched this year, the VHIO Academy manages, integrates and disseminates training opportunities in cancer research, educational initiatives for all VHIO personnel as well as programs tailored to patients and members of our community. Directed by Co-Chairs, Elena Élez and Maria Abad, and headed by Clara Caminal, its main objective is to provide a range of activities aimed at the career development of our faculty and foster a training environment of excellence.

Just some of these programs include institutional fellowships to attract and retain research talents in oncology, continuous learning opportunities such as complementary courses, workshops, seminars and educational events.

In 2021 our first institutional doctoral fellowships call included five four-year FPI-Severo Ochoa grants for national and international young researchers to carry out their doctoral thesis research at our Institute. Associated with our recent accreditation as a Severo Ochoa Center of Excellence, these opportunities are within the framework of the EU Pre-doctoral training contracts (FPI) 2021, and supported by the Spanish Ministry of Science and Innovation.


Spin-off successes

Laura Soucek, Co-Director of VHIO’s Preclinical & Translational Research Program, Principal Investigator of our Models of Cancer Therapies Group, an ICREA Research Professor, and Co-Founder & Chief Executive Officer of VHIO-born spin-off Peptomyc S.L.

Co-founded in 2014 by VHIO’s Laura Soucek, CEO of the enterprise, and Marie-Eve Beaulieu, Chief Scientific Officer (CSO) of the company, VHIO-born spin-off Peptomyc has now received approval from the Spanish Agency of Medicines and Medical Devices for conducting clinical trials in Spain (AEMPS), to initiate the first-in-human Phase I/IIa clinical trial with its first compound – a disruptive Myc inhibitor, Omomyc (OMO-103).

Building on the proven preclinical efficacy and safety of the Omomyc cell-penetrating mini-protein in mouse models, and Peptomyc’s company’s successful development of anti-Myc peptides for the treatment of several tumor types, this latest milestone, celebrated in March 2021, represents a greatly anticipated leap into the clinical research setting, and an important step forward in becoming the first ever clinically viable and direct inhibitor of Myc – a protein implicated in the formation of most tumor types.

MYC has been considered an ‘undruggable’ cancer target for many years. Laura’s group has previously shown that Myc blockade has an excellent therapeutic effect in several mouse models, with mild side effects that are well tolerated and reversible. Now that Laura and her Peptomyc team have received approval to initiate their early phase clinical trial, they can further progress in testing the safety and efficacy of this Omomyc-based therapy for the benefit of cancer patients.

Their Phase I/IIa Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours - MYCure (NCT04808362), led by VHIO’s Elena Garralda, Principal Investigator of our Early Clinical Drug Development Group, and Director of our Research Unit for Molecular Therapy of Cancer (UITM) –CaixaResearch, is now underway.

This study is an open label, two-part, FIH phase I/IIa dose-finding study designed to determine the safety, tolerability, PK, PD and proof-of-concept of OMO-103 in patients with advanced solid tumors:
Part I: Around 11 to 24 patients in total will be enrolled, covering 6 OMO-103 dose levels, with the primary objective of determining the safety and tolerability of OMO-103, and defining an appropriate dose for further evaluation in part IIa.
Part IIa: Dose expansion where at least 3 parallel groups of patients with advanced non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC), will be treated with the recommended phase II dose of OMO-103 to further characterize the safety, tolerability, PK, PD and anti-tumor activity of OMO-103. Approximately 18 patients will be enrolled in each of the 3 parallel groups of patients (NSCLC, PDAC, CRC).


Spin-off successes

Joan Seoane, Co-Director of VHIO’s Preclinical & Translational Research Program, Principal Investigator of our Gene Expression & Cancer Group, an ICREA Research Professor, and Co-Founder of Mosaic Biomedicals.

VHIO’s Joan Seoane and his Gene Expression & Cancer Group previously established the role of leukemia inhibitor factor (LIF) in oncogenesis as a promoter of cancer progression by regulating the tumor microenvironment and inducing self-renewal in tumor-initiating cells. This research culminated in the development of MSC-1, a therapeutic LIF neutralizing antibody. MSC-1’s transition to the clinic and translation into benefits for cancer patients promises an important addition to the current arsenal of powerful anti-cancer weaponry.

Joan co-founded VHIO-born spin-off Mosaic Biomedicals in 2012 for the design and development of this novel compound. In 2016, Mosaic merged with Northern Biologics Inc. (Toronto, Canada), and Northern-Mosaic announced the global acquisition of clinical-stage MSC-1 (now AZD0171) by MedImmune/AstraZeneca in 2020.

The phase II clinical trial of AZD0171 (in combination with durvalumab and chemotherapy) in solid tumors (NCT04999969) initiated patient recruitment in 2021.


At VHIO we are devoted to translating our research into improved clinical outcomes for the direct benefit of cancer patients. To do so, the creation of new spin-off companies is instrumental in developing potential new treatment avenues discovered in the laboratory, and further accelerating our drug discovery efforts.

Created in 2021, and officially launched as this scientific report goes to print, a new spin-off, ONIRIA Therapeutics, comprises three co-founding partners: VHIO, the Universidad de Barcelona (UB), and the ICREA Catalan Institution for Research, and is mainly funded by the ”la Caixa” Foundation, Asociación Española Contra el Cáncer – AECC (Spanish Association Against Cancer), and the Instituto de Salud Carlos III – ISCIII (Institute of Health Carlos III):

Left to Right: Héctor G. Palmer, Principal Investigator, Stem Cells & Cancer Group, Co-Founder and Chief Scientific Officer, ONIRIA Therapeutics. Esther Riambau, Chief Executive Officer, ONIRIA Therapeutics.

By modulating cell dormancy to overcome cancer persistence, this spin-off will develop new anti-cancer armory to counteract resistance and prevent disease relapse in patients. Among various ongoing projects, ONIRIA Therapeutic’s most advanced agent is a first-in-class molecule, ONR-001, that allosterically activates the TET2 master epigenetic enzyme, causing tumor cells to enter a dormant state and even die.

ONIRIA has already secured patent protection for its TET2 modulators and demonstrated efficacy in preclinical animal models by showing that ONR-001 promotes and sustains cancer cell dormancy and even causes cell death upon prolonged treatment. The investigators are now evaluating the efficacy of ONR-001 in several hematologic and solid tumor types, honing in on those cancers that are hypermethylated as a consequence of TET2 loss-of-function.

Héctor G. Palmer, Principal Investigator of VHIO's Stem Cells & Cancer Group, is ONIRIA’s Chief Scientific Officer, and Esther Riambau, a venture builder, serves as the company’s Chief Executive Officer. The founding team also includes Isabel Puig, a Senior Investigator of Héctor’s group, as the company’s Scientific Advisor for new therapeutic targets; Xavier Barril, an ICREA investigator at UB, and ONIRIA’s Scientific Advisor in computational chemistry; Carlos Galdeano, a Serra Hunter Lecturer Professor and Head of the Protein Degradation Laboratory at UB, who is appointed as its Scientific Advisor in drug discovery.


Recognitions and prized research in 2021

Reflective of their exceptional contributions to cancer science, VHIO’s Josep Tabernero, Enriqueta Felip & Javier Cortés featured among Clarivate’s Highly Cited Researchers 2021

In addition to all our newly funded research lines and programs in 2021, also driven through the backing received each year from our Institutional Supporters, and public and private national, European, and International funding sources and entities, VHIO investigators and teams have also been recognized through several prizes, accolades and recognitions.

Just some of which include the following:

VHIO’s trio of Clarivate Highly Cited Researchers 2021. Left to Right: Josep Tabernero, Enriqueta Felip, and Javier Cortés.

For another consecutive year, our Director Josep Tabernero, Enriqueta Felip, Principal Investigator of VHIO’s Thoracic Tumors & Head and Neck Cancer Group, and Javier Cortés, an Associate Translational Investigator at VHIO, featured among Clarivate’s annual listing of some 6,600 Clarivate Highly Cited Researchers in 2021, curated by the Institute of for Scientific Information.

Josep Tabernero, also Head of the Medical Oncology Department, Vall d’Hebron University Hospital (HUVH), has for the sixth consecutive year been selected for significantly advancing cancer research under the category of Clinical Medicine that listed a total of 453 named leaders this year.

Joining Josep on the 2021 list of outstanding contributors to Clinical Medicine, is VHIO’s Enriqueta Felip, Head of the Thoracic Cancer Unit at HUVH, President of the Spanish Society of Medical Oncology (SEOM), and Secretary of the International Association for the Study Lung Cancer (IASLC), who has been recognized for a third year running.

Included under the Cross-Field category last year, Javier Cortés, an Associate Translational Investigator at VHIO, featured as a Highly Cited Researcher 2021 under the same category.


In parallel with the publication of its 2025 Vision, the European Society for Medical Oncology (ESMO) finalized its 2021 composition of expert committees and working groups. These include several VHIO Investigators and Medical Oncologists who were (re) appointed as ESMO serving officers, faculty, committee and editorial board members.

Left to right: Maria Alsina, Judith Balmaña, Irene Braña, Javier Cortés, Elena Garralda, Teresa Macarulla, Ana Oaknin, César Serrano, Cristina Suárez, and Claudia Valverde.

In addition to their existing commitments including contributions at ESMO congresses and conferences as co-organizers, track chairs, expert speakers, discussants and panelists, newly appointed roles in 2021 include the following:
Maria Alsina, a Medical Oncologist and Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla), commenced her mandate as an ESMO Faculty Member, Gastrointestinal Tumours - Upper Digestive, and also serves on Annals of Oncology’s Editorial Board.

Judith Balmaña, Principal Investigator of VHIO’s Hereditary Cancer Genetics Group, is now a Member of ESMO’s Cancer Prevention Faculty. She also continues to serve as a Faculty Coordinator of ESMO’s Cancer Genetics Group and collaborates in the compilation and updating of its Clinical Practice Guidelines.

Irene Braña, Clinical Investigator and Medical Oncologist of VHIO’s Thoracic Tumors & Head and Neck Cancer Group (PI: Enriqueta Felip), is an appointed member of ESMO’s Neck Cancer Faculty.

In addition to his membership of ESMO’s Scientific Committee and chairmanship at several ESMO congresses meetings, and his appointment as Editorial Board Member of its top journal Annals of Oncology, Javier Cortés, Associate Translational Investigator at VHIO, also serves as Member of its Breast Cancer Faculty.

Elena Garralda, Principal Investigator of our Early Clinical Drug Development Group, and Director of our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, is now a Member of its Developmental Therapeutic Faculty, and continues to serve as a Core Member of ESMO’s Women for Oncology Committee. Elena is also author of the ESMO Perspectives digital magazine’s On target column. Further enriching the magazine’s appeal and illuminating potentially controversial issues and emerging trends in cancer research and clinical practice, On target launched in 2021.

Teresa Macarulla, Principal Investigator, VHIO’s Gastrointestinal & Endocrine Tumors Group, now serves as an Editorial Board Member of ESMO’s flagship journal, Annals of Oncology .

Ana Oaknin, Principal Investigator of VHIO’s Gynecological Malignancies Group is appointed as an ESMO Guidelines Committee Subject Editor, and also serves as a Gynecologic Cancer ESMO Faculty Member.

César Serrano, Principal Investigator of VHIO’s Sarcoma Translational Research Group, and Claudia Valverde, Clinical Investigator and Medical Oncologist, VHIO’s Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group (PI: Joan Carles), are both Members of ESMO’s Sarcoma Faculty.

Cristina Suárez, Medical Oncologist and Clinical Investigator, VHIO’s Genitourinary, CNS Tumors & Cancer of Unknown Primary Site Group (PI: Joan Carles) has been appointed as a Member of ESMO’s Genitourinary Tumors, Non-Prostate Faculty.

Expanding their commitments to ESMO, they join previously appointed VHIO faculty who are current members of ESMO Committees, Task Forces, and Editorial Boards, including our Director, Josep Tabernero, who is Past-President of ESMO (2018-2019), Member the Magnitude of Clinical Benefit Scale Working Group, Core Committee Member of ESMO’s European Policy Committee, and an Associate Editor of Annals of Oncology and ESMO Open.


Enriqueta Felip, Principal Investigator, VHIO’s Thoracic Tumors & Head and Neck Cancer Group.

Having served as Vice-President of the Spanish Society of Medical Oncology’s (SEOM) throughout its previous two-year term of governance, VHIO’s Enriqueta Felip has now taken the reins as SEOM’s new President (2021-2023). Officially announced at its Annual virtual SEOM Congress 2021, she continues to serve alongside its Board of Directors, expert committees, working groups and supporters, to respond to the rapidly changing needs of its membership and further establish SEOM as a leading professional society in medical oncology.

Efforts led in tandem by Enriqueta and SEOM’s Vice-President, César Rodríguez, Medical Oncologist, the Salamanca University Hospital, will also focus on promoting the multidisciplinary approach to the diagnosis and treatment of cancer, forging and nurturing key alliances with other professional societies, including the European Society for Medical Oncology (ESMO), and further strengthening SEOM’s presence on the international oncology stage.

Also officially announced and Annual virtual Congress 2021, César Serrano, Principal Investigator of VHIO’s Sarcoma Translational Research Group, now serves as a SEOM Board Member. Dedicated to identifying and responding to the needs of young oncologists in Spain, Elena Élez, Medical Oncologist and a Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group, continues to coordinate the +MIR SEOM Residents and Young Oncologists Committee. Elena’s devotion to nurturing and growing the careers of young investigators and medical oncologist is also reflected by her co-leadership of VHIO’s recently established Academy.


The 2020 and 2021 recpients of the prestigious ICS Research Awards.

Celebrated during the Institut Català de la Salut (Catalan Institute of Health - ICS) 2021 Annual Conference on research developments at ICS and around the world, the recipients of the 2020-2021 ICS Research Awards included our Director, Josep Tabernero, and Garazi Serna, a PhD Student of VHIO’s Molecular Oncology Group (PI: Paolo Nuciforo). Due to the safety issues posed by COVID-19, in-person attendance was naturally limited to a minimum, and this year’s meeting also included the 2020 ICS Research Award winners who were not presented with these prestigious recognitions last year due to the pandemic. Josep Tabernero, Head of the Medical Oncology Department at the Vall d’Hebron University Hospital (HUVH), received the ICS 2020 Lifetime Achievement Award for Research in Hospitals of the Catalan Institute of Health. This accolade recognizes his outstanding contributions to advancing precision medicine in oncology, especially in colorectal cancer. Under the predoctoral category, the 2021 ICS prize for the best research paper in Health Sciences was awarded jointly to VHIO’s Garazi Serna and Juan Carrillo, a Student at the Childhood Liver Oncology Group, led by Carol Armengol, the Germans Trias i Pujol Institute, (IGTP).

Garazi Serna, a PhD Student of VHIO’s Molecular Oncology Group (PI: Paolo Nuciforo).

Garazi Serna’s awarded research*, carried out in collaboration with other VHIO investigators, advanced insights into the role of Fusobacterium nucleatum, an important pathogenic gut bacterium associated with colorectal cancer, in locally advanced rectal cancer (LARC). By quantifying Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients, the investigators sought to establish its association with response to therapy and survival. First authored by Garazi Serna, this study showed that F. nucleatum persistence post-nCRT is associated with high relapse rates, potentially linked to suppression of immune cytotoxicity. These findings could help to more precisely identify a higher risk of disease recurrence or metastasis in patients who do not show a complete response to treatment, and ultimately support clinical decision-making.


*Serna G, Ruiz-Pace F, Hernando J, Alonso L, Fasani R, Landolfi S, Comas R, Jimenez J, Elez E, Bullman S, Tabernero J, Capdevila J, Dienstmann R, Nuciforo P. Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer. Ann Oncol. 2020 Oct;31(10):1366-1375.


VHIO was prized with the I Premio José Baselga a la Innovación Traslacional en Oncología at the 9th annual edition of the Fundación para la Excelencia y la Calidad de la Oncología ECO Awards.

At the 9th annual edition of the Fundación para la Excelencia y la Calidad de la Oncología - ECO Awards (Foundation for Excellence and Quality in Oncology), celebrated at the Royal Academy of Medicine, Madrid (Spain), VHIO received ECO’s first Premio José Baselga a la Innovación Traslacional en Oncología (José Baselga Prize for Translational Innovation in Oncology). This prize, honoring the tremendous legacy of our founding and first director, José Baselga, who very sadly died at the age of 61 on 21 March 2021, recognizes excellence in translational cancer research and precision oncology.

In his acceptance speech, broadcast live during the ceremony, our Director, Josep Tabernero, thanked the ECO Foundation for establishing this special Award as a tribute to José Baselga’s extraordinary accomplishments and illustrious career. He also dedicated the prize to all VHIO Faculty who strive to honor José’s legacy by applying the same dedication, determination, collaborative spirit and fight in solving cancer sooner.


One of our Patrons and Institutional Supporters, the Fundación FERO – whose founder and late Honorary President is José Baselga who tragically passed away this year (see our Director’s Foreword), announced its 2021 Annual Award winners back in May.

These prestigious accolades include FERO’s Awards for Translational Research, now in their 21st edition in 2021, and the third FERO-ghd Award for breast cancer research. Most recently, as this scientific report goes to print, FERO announced its Dr. Baselga Award to further promote translational research in oncology. This prize, honoring the extraordinary life and scientific legacy of José Baselga, VHIO’s founder and first director, will spur translational research of excellence carried out at research institutes in Spain by investigators of any nationality.

VHIO-led projects prized by FERO in 2021

In addition to FERO’s championing of our Advanced Molecular Diagnostics Program – DIAMAV, and several other VHIO investigators and groups, the following projects will be fueled by FERO’s support:

Nicolas Herranz, Senior Investigator of our Prostate Cancer Translational Research.

Nicolas Herranz, Senior Investigator of our Prostate Cancer Translational Research directed by Joaquin Mateo, was awarded by FERO this year for his project entitled, Exploiting therapy-induced senescence in a synthetic lethal approach to treat advanced prostate cancer. Thanks to this support received through this Award, Nicolas will pursue research aimed at identifying new therapies or drug combinations that neutralize senescent cells and prevent cancer resistance in prostate cancer.

Specifically, his project will focus on the modulation of prostate cancer evolution by harnessing the emergence of a senescence phenotype (via treatment with standard-of-care or targeted therapies) to then target with senolytic drugs under a synthetic susceptibility approach.

He will seek to characterize therapy-induced senescence (TIS) phenotype in response to androgen receptor signalling inhibition or targeted drugs in prostate cancer cell lines; identify senolytic drugs highly selective for TIS prostate cancer cells by screening customized drug libraries; validate the efficacy of the identified drug combinations in patient-derived xenograft (PDXs) models; evaluate TIS in patient biopsies collected on response to therapy; and pioneer the characterization of TIS signatures in PC by combining transcriptomic data of PC cell lines and patient samples.

This FERO Award was supported by the Ramón Areces Foundation. Due to the safety issues posed by the COVID-19 pandemic, FERO’s XXI Annual Awards were officially announced via a live streamed special session.


Two additional VHIO projects received funding from the FERO Foundation in 2021:

Josep Tabernero, VHIO’s Director and Head of the Medical Oncology Department, Vall d’Hebron University Hospital (HUVH).

Led by Josep Tabernero, a newly -funded project on New technologies for the identification of markers of sensitivity and resistance to targeted therapies in metastatic colorectal cancer, will seek out de novo and acquired sensitivity/resistance mechanisms in patients with metastatic colorectal cancer harboring a BRAF mutation. Aimed at developing new therapeutic strategies to more effectively treat this disease, this project will strive to improve cancer treatment selection in this patient population.

The investigators will also assess the value of BRAF V600E Mutant Allele Frequency (MAF), in circulating cell-free DNA (cfDNA) as a biomarker to predict treatment response, as well as a potential tool for the selection of the treatment.

Joan Seoane, Co-Director of VHIO’s Preclinical & Translational Research Program, Principal Investigator of our Gene Expression & Cancer Group, an ICREA Research Professor.

Joan Seoane has received funding for his project entitled: Liquid biopsy in pediatric brain cancer: circulating DNA analysis in cerebrospinal fluid in medulloblastoma pediatric patients with medulloblastoma to help in the detection, characterization and treatment of brain tumor recurrence.

Focused on circulating DNA in cerebrospinal fluid in pediatric patients with medulloblastoma suspected of relapse, research could help to detect disease relapse earlier, differentiate recurrence from false progression, and facilitate the design of more effective therapies to improve patient outcomes.

Analyzing cerebrospinal fluid and tumor DNA in blood is a much less invasive and sequential way of studying these tumors, and allows for the more precise tracking of disease to better guide molecular diagnosis, prognosis and, above all, treatment decision making.

Joan and his team, will study 25 pediatric patients with progression by analyzing circulating DNA in cerebrospinal fluid. This research is based on the close monitoring of patients to detect possible disease relapse which is the main cause of mortality in these patients due to the complexities associated with obtaining tumor tissue samples.


In addition to its support of many other VHIO programs and initiatives, including our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, and our CaixaResearch Advanced Oncology Research Program, four new VHIO projects received funding in 2021 from one of our Institutional Supporters and patrons, the ”la Caixa” Foundation:

Elena Élez, Medical Oncologist and Clinical Investigator of our Gastrointestinal & Endocrine Tumors Group.

First, thanks to an awarded Health Research ”la Caixa” Project, Elena Élez will lead the PROMISE study: BioPrinted hydROgel MicrofluIdicS to mimic patient-specific tumor mEtastatic. Coordinated by the Institut de Bioenginyeria de Catalunya – IBEC (IBEC Institute for Bioengineering of Catalonia), this project will apply 3D bioprinting technology aimed at improving the survival of cancer patients.

3D bioprinting techniques generate three-dimensional cell models that replicate human physiology to test new therapeutic strategies in the laboratory. These models can effectively mimic a patient’s specific tumor and tumor microenvironment. By combining 3D bioprinting with advanced liquid biopsy technology in an organ-on-a-chip system, this novel approach will provide physicians with new tools to better understand and monitor disease evolution in patients with metastatic colorectal cancer, and improve survival rates.


Supported by the ”la Caixa” INPhINIT Retaining and INPhINIT Incoming Fellowship Programs, a trio of predoctoral projects have also been granted this year.

INPhINIT Retaining:

Olivia Prior, PhD Student, VHIO’s Radiomics Group.

Under the mentorship of Raquel Perez-Lopez, Principal Investigator of our Radiomics Group, Olivia Prior’s project, Deciphering spatial and temporal cancer heterogeneity by applying machine learning and precision imaging, aims to accurately characterize the spatial-temporal landscape of intratumor heterogeneity by 3-dimensional (3D) computed tomography (CT) and magnetic resonance imaging (MRI) radiomics. Olivia will also integrate radiomics with molecular data from tumor samples and circulating tumor DNA, through the application of multi-omics. This approach may improve tumor characterization, response assessment and help to more precisely guide treatment selection.


Marion Martínez, Graduate Student, VHIO’s Cellular Plasticity & Cancer Group.

Mentored by Maria Abad, Principal Investigator of VHIO’s Cellular Plasticity & Cancer Group, Marion Martínez will carry out her research project entitled, OncoPeptides: mining the secreted microproteome for novel regulators of PDAC biology, which is based on the hypothesis that exosome-packaged microproteins are essential messengers for tumor communication both within the primary tumor site and distantly within the pre-metastatic niche, and thus regulate tumor progression and cancer cell spread. Focused on pancreatic adenocarcinoma (PDAC), Marion will seek to mine its exosome-secreted microproteome for novel regulators of cancer growth and metastasis.


INPhINIT Incoming:

Ariadna Grinyó, Graduate Student, VHIO’s Growth Factors Group.

Under the mentorship of Joaquín Arribas, Principal Investigator of our Growth Factors Group, Ariadna Grinyó’s research project, Armoring a p95HER2 CAR T for the controlled secretion of antitumor agents upon T-cell activation, will build on previous research of this group that led to the development of a second-generation CAR T against p95HER2, a tumor-specific antigen expressed in around 30% of HER2+ tumors.

Results demonstrated its high effectivity and specificity in vivo against p95HER2 positive cell line-derived tumors, but limited antitumoral effect in patient-derived xenograft (PDXs) models (unpublished). In addition, the general failure of second-generation CAR T s against solid tumors in the clinic illuminates the need to improve the design of therapies. Ariadna will focus on the design and testing of an armored p95HER2 CAR T for the controlled secretion of antitumor agents upon T-cell activation.


The Asociación Española Contra el Cáncer – AECC (Spanish Association against Cancer), is a longstanding supporter of several VHIO groups and researchers. We take this opportunity to salute and applaud AECC’s invaluable contribution to promoting cancer discovery and translational research of excellence, as well as the essential backing that it provides to countless investigators and teams across Spain and beyond.

Additional VHIO researchers were awarded this year across four of AECC’s many pioneering programs and initiatives. In 2021, VHIO’s Maria Abad, Joaquin Mateo, and Raquel Perez-Lopez, received funding as an AECC Coordinated Group, Carolina Ortiz as an AECC Junior Clinician, Isabel Puig as an AECC Researcher, and Enrique Javier Arenas as an AECC Postdoc.

Left to right: María Abad, PI of VHIO’s Cellular Plasticity & Cancer Group, Joaquin Mateo, PI of our Prostate Cancer Translational Research Group, and Raquel Perez-Lopez, PI of VHIO’s Radiomics Group.

Awarded under the category of AECC Coordinated Group – National Consortium, María Abad, Joaquin Mateo, and Raquel Perez-Lopez, Principal Investigators of VHIO’s Cellular Plasticity & Cancer, Prostate Cancer Translational Research, and Radiomics Groups, respectively, will lead a project entitled, Tumoral senescence induced by anti-cancer therapies constitutes a novel prognostic biomarker and a therapeutic target.

This consortium comprises experts in preclinical, translational and clinical research to investigate therapy-induced senescence (TIS) as a new prognostic biomarker and therapeutic target, and develop novel therapeutic strategies and non-invasive diagnostic tools. This project focuses on pancreatic and prostate cancer; two tumor types with robust preclinical evidence of therapy-induced senescence, and in critical need for new, more effective therapeutic options.

Experts in cellular senescence, diagnostic medical imaging, and the development of new therapies, will work together to develop non-invasive imaging methods to detect senescence in tumors, and identify new targets and, eventually, new compounds or combinations that neutralize senescent cells to avoid their undesirable effects on residual tumors post-therapy. In short, the investigators will strive to drive the concept of cellular senescence closer to the clinic.


Carolina Ortiz, Clinical Investigator and Medical Oncologist, VHIO’s Breast Cancer Group.

Awarded this year as an AECC Junior Clinician, Carolina Ortiz will investigate Circulating tumor DNA (ctDNA) in breast milk for the early detection of pregnancy pregnancy-associated breast cancer, led by Cristina Saura, Principal Investigator of our Breast Cancer Group.

Based on their previous studies showing that ctDNA could be isolated from breast milk in 10 patients with pregnancy-associated breast cancer, including patients with early-stage disease, and that tumor mutations were also present in ctDNA isolated from breast milk, the researchers propose that the detection of ctDNA in breast milk can be used as a new non-invasive biomarker for the early diagnosis of breast cancer associated with pregnancy.

The main objectives of this new study are to quantify the ctDNA and the mutant allelic fraction in breast milk, and assess the sensitivity, specificity and precision of the detection of ctDNA in breast milk and blood. Directed by Cristina Saura, Carolina Ortiz will co-conduct a case-control study that includes patients with pregnancy-associated breast cancer (cases) and pregnant patients at a higher risk of developing breast cancer. For the detection of ctDNA, the researchers will combine state-of-the-art sequencing techniques and panels of specific BRCA genes. Mutations detected in breast milk will be compared with blood and tumor samples from the same patients.


Isabel Puig, Post-Doctoral Fellow, VHIO’s Stem Cells & Cancer Group.

Isabel Puig was awarded under the category of AECC Investigator, for a project aimed at Deciphering the molecular mechanisms of tumor cell resistance to cancer therapies, directed by Héctor G. Palmer, Principal Investigator of VHIO’s Stem Cells & Cancer Group.

The resistance of tumor cells to anti-cancer medicines represents a major challenge in more successfully combating cancer. This therapeutic failure is due to the multiple strategies that cancer cells adopt to dodge therapeutic blows. Disrupting multiple resistance strategies at once has emerged as a promising approach toward successfully eradicating these resistant malignant cells as major drivers of disease relapse.

This group has previously identified a new actor that can simultaneously regulate several of these resistance strategies. Isabel Puig’s awarded project will seek to develop a novel therapy to more effectively thwart disease recurrence, and advance deeper insights into the molecular mechanisms that are implicated in tumor cell resistance to cancer therapies.


Enrique Javier Arenas, Post-Doctoral Fellow, VHIO’s Growth Factors Group.

Selected under the AECC Postdoc funding category, VHIO’s Enrique Javier Arenas will pursue research focused on Overcoming cancer immunotherapy resistance: new combinatorial strategies to improve immunotherapies, directed by Joaquín Arribas, Principal Investigator of our Growth Factors Group.

This group’s previous studies have established models of resistance to T-cell based therapies and identified a novel mechanism of resistance. They evidenced that disruption in interferon-gamma signaling in cancer cells leads to intrinsic resistance to destruction by fully active, correctly engaged, T lymphocytes.

Based on these findings, this project aims at identifying novel strategies that could be rapidly applied in the clinic, further exploring the mechanistic biology of resistant cells and the interplay with interferon-gamma response and resistance to immunotherapy.


The 2021 Sociedad Española de Oncología Médica (SEOM) Award Ceremony.

In celebration of this year’s awardees who were granted by the Sociedad Española de Oncología Médica – SEOM (Spanish Association of Medical Oncology), the in-person Award Ceremony took place but with a limited attendance due to the safety issues posed by the COVID-19 pandemic. Announced on the occasion of SEOM’s virtual Annual Congress – SEOM2021, the 44 prized projects included a duo of VHIO proposals aimed at improving outcomes for breast cancer patients.

Left to right: VHIO’s Cristina Saura and Mafalda Oliveira, recipients of SEOM Awards in 2021.

Cristina Saura, Principal Investigator of our Breast Cancer Group, was presented with the SEOM-Daiichi Sankyo Award for her project on ctDNA in breast milk for the early detection of pregnancy-associated breast cancer.

These patients generally have a poor prognosis since they are usually diagnosed at late-stage. The physiological changes that occur in the breast make it difficult to palpate to identify nodules. Furthermore, during pregnancy cancer is not usually actively searched for.

After analyzing samples of breast milk from patients who had been diagnosed with breast cancer, Cristina’s team previously discovered the presence of circulating tumor DNA (ctDNA). Their hypothesis is that tumors in their earliest stages are very small and have not released enough ctDNA into the bloodstream. But, due to the proximity of the breast tissue to the tumor, there is a high amount ctDNA in breast milk for the early detection of pregnancy-associated breast cancer, which would improve the prognosis of these patients.

Reflective of the novelty of this approach, this VHIO-led research has also been awarded this year by the Asociación Española Contra el Cáncer – AECC (Spanish Association against Cancer), and also previously received funding through the joint Fundación FERO (FERO Foundation)-ghd annual Award in 2020.


Mafalda Oliveira, a Clinical Investigator and Medical Oncologist of Cristina Suara’s Breast Cancer Group, received the SEOM – FECMA/MASET Award for research Exploring the impact of breast and gut microbiome on breast cancer prognosis and response to immune checkpoint inhibitors. This project is based on earlier research led by other VHIO groups that evidenced how the intestinal microbiota plays an important role in colorectal cancer.

Considering these results, research led by Mafalda will seek to establish if the mammary microbiota also plays a role in breast cancer. The investigators will study how, together with the gut microbiome, it can influence the response to treatment with immune checkpoint inhibitors (ICIs), considering that the microbiota plays essential roles in the immune response.


VHIO’s Director, Josep Tabernero, receiving a 2021 Trifermed Award for Social Impact in Healthcare.

Trifermed Annual Awards recognize individuals and organizations that make significant contributions to improving the quality of healthcare in our society. Prized under the Impulsor category, our Director, Josep Tabernero, was recognized in 2021 for his outstanding achievements in advancing precision medicine in oncology and improving outcomes for cancer patients. This year’s Trifermed Award Ceremony took place in person, with a limited attendance to comply with COVID-19 safety measures and regulations.

In his acceptance speech, Josep paid tribute to people who have lost their loved ones to COVID-19, as well as all healthcare professionals who worked tirelessly to overcome the major challenges that it posed throughout the pandemic waves. He dedicated this Award to all oncology professionals at the Vall d’Hebron University Hospital (HUVH), and VHIO’s multidisciplinary research teams. He also gratefully thanked several other leaders within the field, including the eminent cancer researcher and trailblazing medical oncologist, José Baselga, VHIO’s founder and first director, who very sadly died last year at the age of 61.


Broadcast live during Merck’s Research Awards Ceremony, our Director, Josep Tabernero, dedicated this recognition to all healthcare professionals in oncology at the Vall d’Hebron University Hospital (HUVH), as well as VHIO’s researchers and clinical investigators.

Marking the 30th Anniversary of the Fundación Merck Salud (Merck Health Foundation), its annual Ayudas Merck de Investigación 2021 (Merck Research Awards) were presented at the Teatro Real in Madrid (Spain). These recognitions support pioneering research projects spanning endocrinology and/or cardiometabolic risk, rare diseases, multiple sclerosis, fertility, immune-oncology, and personalized precision medicine.

This year’s Award Ceremony, celebrated in person albeit with a reduced participation due to the safety issues posed by COVID-19, also recognized five leading figures in Spanish healthcare and institutions of excellence including Josep Tabernero, VHIO’s Director and Head of the Medical Oncology Department at the Vall d’Hebron University Hospital (HUVH).

Josep dedicated this important recognition to all healthcare professionals and teams who provide cancer patients with the very best treatment and care, as well as VHIO researchers who strive to improve patient outcomes by advancing cancer discovery and clinical researh. Most importantly, he recognized the generosity of patients and thanked them for their amazing support of - and belief in - our cancer research.


Laura Escudero, a Post-Doctoral Fellow of Joan Seoane’s Gene Expression & Cancer Group.

Laura Escudero, a Post-Doctoral Fellow of VHIO’s Gene Expression & Cancer Group, received a Scientific Innovation Award for Young Researchers from the Fundación Pfizer (Pfizer Foundation), for research focused on cerebrospinal fluid as liquid biopsy for the precise characterization and policing of medulloblastoma.

Building on previous research led by Joan Seoane, Laura first authored a proof-of-concept study* showing that the analysis of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA), allows for the more precise characterization, molecular diagnosis (including subtyping and risk stratification), and real time tracking of medulloblastoma – the most prevalent malignant brain tumor in childhood.

Carried out in collaboration with other VHIO groups and experts at the Vall d’Hebron University Hospital, the investigators showed that ctDNA from cerebrospinal fluid reveals genomic alterations during disease evolution (even prior to surgery) to more precisely guide treatment decision making. This approach also translates in less invasive sampling and better identification and characterization of disease relapse.

In recognition of this pioneering research, this Fundación Pfizer Prize will further support Laura Escudero to pursue her research and develop her career.


* Escudero L, Llort A, Arias A, Diaz-Navarro A, Martínez-Ricarte F, Rubio-Perez C, Mayor R, Caratù G, Martínez-Sáez E, Vázquez-Méndez É, Lesende-Rodríguez I, Hladun R, Gros L, Ramón Y Cajal S, Poca MA, Puente XS, Sahuquillo J, Gallego S, Seoane J. Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma. Nat Commun. 2020 Oct 27;11(1):5376.


Left to right: Violeta Serra, VHIO’s Violeta Serra, Principal Investigator of our Experimental Therapeutics Group. Violeta Serra presenting her prized Metapremio research project in the Auditorium of our CELLEX Building.

Research directed by VHIO’s Violeta Serra, Principal Investigator of our Experimental Therapeutics Group, was prized with a 2021 Metapremiofrom the Asociación de Cáncer de Mama Metastásico (Spanish Association against Metastatic Breast Cancer) for a research project aimed at identifying biomarkers of response to a novel antibody-drug conjugate (ADC), using breast cancer patient-derived xenograft models (PDXs).

Violeta’s research will further build on the first results of a window of opportunity trial, SOLTI-1805 TOT-HER3, co-led by VHIO’s Mafalda Oliveira, Clinical Investigator and Medical Oncologist of Cristina Saura’s Breast Cancer Group. TOT-HER3 is the first study to evaluate the HER3-directed antibody-drug conjugate (ADC), patritumab deruxtecan, in patients with early hormone-sensitive HR-positive/HER2-negative breast cancer.

Aimed at identifying biomarkers of treatment response to better predict which patients would be most likely to benefit from this ADC, Violeta and her team will build on their preclinical studies that complemented the biomarker findings of TOT-HER3 using metastatic breast cancer patient-derived xenografts (PDXs) models. The investigators will now evaluate the activity of this ADC in clinically relevant PDX models, derived from patients who progressed on CDK4/6 or PARP inhibitors (PARPi). They will also aim to dissect its mode of action to help identify biomarkers for the selection of patients in clinical practice.

The Spanish Association against Metastatic Breast Cancer was created thanks to the dedication of Chiara Giorgetti, a former patient of VHIO’s Cristina Saura, alongside other patients with metastatic breast cancer and their friends and families. When Chiara sadly passed away from metastatic breast cancer in December 2018, this Association established the Chiara Giorgetti Award in 2019, and later, the Metapremios, in her memory.


Joaquin Mateo, Principal Investigator, VHIO’s Prostate Cancer Translational Research Group.

In 2021, Joaquin Mateo, Principal Investigator of our Prostate Cancer Translational Research Group, was announced as one of the six recipients of a Fundación Cris contra el Cáncer (CRIS Foundation against cancer) Clinical Talent Program Award. Aimed at providing support and incentives for clinical researchers to develop their careers in Spain, this five-year funding program will enable Joaquin to develop and advance his research lines carried out at VHIO and the Vall d’Hebron University Hospital.

This funding will support research into Prostate cancer genomic evolution and signatures of DNA damage repair deficiencies. Building on his group’s previous studies aimed at optimizing the use of PARP inhibitors (PARPi) in metastatic prostate cancer (mPC), Joaquin and his team will seek to further refine the optimal biomarker suite for patient stratification toward potentially expanding the target population who can benefit from these promising anti-cancer medicines.

At the genomic level, the investigators will study hundreds of samples of prostate tumors at different stages. They will assess how and when alterations appear that render these tumors vulnerable to PARPi. These efforts will help to more precisely identify those patients who would be most likely to respond to these treatments, and better guide clinical decision making.


Left to right: Francisco Javier Ros, Clinical Investigator and Medical Oncologist, VHIO’s Gastrointestinal & Endocrine Tumors Group. Francisco upon receiving his Fundación Mutual Médica Award in 2021.

Now in their 31st annual edition, the Fundación Mutual Médica (Mutual Médica Foundation) Awards recognize the important contributions made by physicians, residents and students in developing innovative therapies, advancing diagnostic tools and platforms, and advancing the treatment and care of patients.

Under the mentorship of Elena Élez, Francisco Javier Ros, Clinical Investigator and Medical Oncologist of our Gastrointestinal & Endocrine Tumors Group, was awarded for a project entitled, Identification and validation of response and resistance mechanisms to targeted therapies for BRAFV600E mutated metastatic colorectal cancer.

Over recent years, research has greatly advanced insights into the molecular biology of colorectal cancer. While more effective, targeted treatments have improved outcomes for certain patients, a significant number of patients do not respond to treatment or whose disease rapidly progresses. In particular, patients with a BRAFV600E mutation, present in 8-10% of metastatic colorectal cancer (mCRC), have a poor prognosis with limited treatment options.

Carried out in collaboration with Héctor G. Palmer’s Stem Cells & Cancer Group, at VHIO, results in preclinical models revealed that tissue remodelling and mucinous differentiation contribute to the acquisition of resistance to BRAF inhibitor-based therapies. Our investigators will now seek to unveil new vulnerabilities in these tumors, and develop models to test the efficacy of new treatment combinations. They will also evaluate new predictive biomarkers of response to treatment to help better guide the optimal selection of therapy matched to molecular specificities of patients with BRAF V600E-mutated mCRC.


In addition to the examples highlighted here – featuring just some of the many newly funded research lines, initiatives, and programs in 2021 – we invite you to browse our comprehensive listing under New Funding and Projects in 2021, as well as view a complete listing of our Institutional Supporters, public and private national, European, and International funding sources and entities this year.


VHIO-organized events: sharing the latest advances & developments in cancer science and clinical investigation

VHIO is dedicated to organizing events of the highest caliber to present and debate the very latest in cancer discovery – from the bench to bedside and back. These educational opportunities often lead to new research collaborations that continue to accelerate our collective efforts aimed at solving cancer sooner.

Scientific co-Chairs (left to right): María Abad, PI, Cellular Plasticity & Cancer Group, Laura Soucek, PI, Models of Cancer Therapies Group, and Elena Élez, Medical Oncologist and Clinical Investigator, Gastrointestinal & Endocrine Tumors Group. Scientific Coordinator: Josaep Maria Miquel (far right), Senior Project Manager, VHIO’s Scientific Management Area.

Launched back in 2019, our VHIO – CaixaResearch Scientific Seminars Series educational program welcomes internationally renowned researchers and clinical investigators to VHIO to share, discuss and debate latest insights, discovery and next directions in oncology with our students, postdocs and senior faculty from our preclinical, translational and clinical research groups.

These sessions take place in VHIO’s state-of-the-art CELLEX Building Auditorium, although the majority in 2021, were hosted virtually due to the COVID-19 pandemic. Each seminar typically consists of a 30-45 minute talk followed by a Q&A round with the audience. Chaired be each respective VHIO host, these expert talks are usually scheduled to take place on Fridays.

In 2021, a total of 23 VHIO - CaixaResearch Scientific Seminars took place as follows:


  • Speaker: Arkaitz Carracedo, Principal Investigator of Cancer Cell Signaling & Metabolism Lab, CICbioGUNE, Bilbao, Spain
  • Talk title: Metabolic Intricacies of Prostate Cancer
  • Date: 15 January
  • VHIO Host: Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Chi Van Dang, Scientific Director, Ludwig Institute for Cancer Research. Professor, The Wistar Institute, Pennsylvania, USA
  • Talk title: MYC, Metabolism & the Circadian Clock in Tumorigenesis
  • Date: 05 February
  • VHIO Host: Laura Soucek, PI, Models of Cancer Therapies Group

  • Speaker: Elisa Espinet, German Cancer Research Center | DKFZ. Division of Stem Cells and Cancer, Heidelberg, Germany
  • Talk title: Cellular Cross-Talks, Heterogeneity and Cell of Origin of Human PDAC: Insights from the Transcriptome & Methylome of Isolated Cell Populations
  • Date: 05 March
  • VHIO Host: Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Benjamin Neel, Professor of Medicine, NYU Grossman School of Medicine, Director, Laura and Isaac Perlmutter Cancer Center, NY, USA
  • Talk title: New Combination Approaches to Targeting Cancer
  • Date: 19 March

  • Speaker: María Casanova-Acebes, Junior Group Leader at CNIO, Madrid, Spain
  • Talk title: Macrophage Determinants for the Initiation & Progression of Non-Small-Cell Lung Carcinoma
  • Date: 09 April
  • VHIO Host: Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Umberto Malapelle, Chief Supervisor, Predictive Molecular Pathology Laboratory, Department of Public Health, University Federico II of Naples, Italy
  • Talk title: Next Generation Sequencing in Predictive Molecular Pathology
  • Date: 23 April
  • VHIO Host: Paolo Nuciforo, PI, Molecular Oncology Group

  • Speaker: Geoff Lindeman, Joint Head, Cancer Biology & Stem Cells Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
  • Talk title: Searching for Novel Therapeutic Targets for the Treatment & Prevention of Breast Cancer
  • Date: 07 May
  • VHIO Host: Judith Balmaña, PI, Hereditary Cancer Genetics Group

  • Special Session: VHIO Meet the Editors with Miguel Foronda, Associate Editor, Nature Cancer
  • Talk title: The Ins & Outs of Nature Cancer
  • Date: 20 May
  • VHIO co-Hosts: Joan Seoane, PI, Gene Expression & Cancer, and Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Yardena Samuels, Head, EKARD Institute for Cancer Diagnosis Research. Department of Molecular Cell Biology. Head, Weizmann-Brazil Tumor Bank, Rehovot, Israel
  • Talk title: Towards Deciphering the Immuno-Genomic Landscape in Melanoma
  • Date: 21 May
  • VHIO Host: Alena Gros, PI, Tumor Immunology & Immunotherapy Group

  • Speaker: Raquel Sánchez, Head, Service of Neurology, Hospital Clínic de Barcelona. Alzheimer’s disease & other cognitive disorders group. IDIBAPS, University of Barcelona, Spain
  • Talk title: Creutzfeldt-Jakob Disease & Other Prion Diseases
  • Date: 28 May
  • VHIO Host: Laura Soucek, PI, Models of Cancer Therapies Group

  • Speaker: Mercedes Robledo, Group Leader, Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain
  • Talk title: Genetics & Genomics of Pheochromocytomas. Searching for its Achilles Heel
  • Date: 04 June
  • VHIO Host: Judith Balmaña, PI, Hereditary Cancer Genetics Group

  • Speaker: Jean Yves Masson, Full Professor, Laval University Cancer Research Center, Quebec, Canada
  • Talk title: Functional Analysis of Missense Mutations in Homologous Recombination Proteins
  • Date: 18 June
  • VHIO Host: Sara Gutiérrez-Enríquez, Senior Investigator, Hereditary Cancer Genetics Group

  • Speaker: Toni Celiá-Terrassa, Group Leader, Cancer Stem Cells & Metastasis Dynamics Lab, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
  • Talk title: Stem Cell Properties in Breast Cancer Metastasis
  • Date: 02 July
  • VHIO Host: Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Manuel Collado, Group Leader, Stem Cells in Cancer and Aging Laboratory, Health Research Institute of Santiago de Compostela (IDIS), A Coruña, Spain
  • Talk title: Cell Senescence in Development, Regeneration & Cancer
  • Date: 16 July
  • VHIO Host: Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Ephrat Levy-Lahat, Director, Medical Genetics Institute, Professor, Internal Medicine & Medical Genetics, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
  • Talk title: Hereditary Breast Cancer: From Families to the Population
  • Date: 30 July
  • VHIO Host: Judith Balmaña, PI, Hereditary Cancer Genetics Group

  • Speaker: Charles Swanton, Senior Group Leader, Francis Crick Institute & UCL Cancer Institute, London, UK
  • Talk title: Cancer Evolution, Immune Evasion & Metastasis
  • Date: 17 September
  • VHIO Host: César Serrano, PI, Sarcoma Translational Research Group

  • Speaker: Antonia Tomás, Group Leader, Circadian Rhythm and Cancer Laboratory, IMIB-UMU-Arrixaca, Murcia, Spain
  • Talk title: Circadian Rhythm & Cancer: an Approximation with Diurnal Animal Models
  • Date: 01 October
  • VHIO Host: Maria Abad, PI, Cellular Plasticity & Cancer Group

  • Speaker: Marie Arsenian, Professor, Molecular Tumor Biology, Karolinska Institutet (KI), Stockholm, Sweden
  • Talk title: MYCN & Differentiation Control in Childhood Neuroblastoma
  • Date: Friday 13th November, 12:00h
  • VHIO Host: Laura Soucek, PI, Models of Cancer Therapies Group

  • Speaker: Amanda Spurdle, NHMRC Investigator Fellow, Group Leader, Molecular Cancer Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • Talk title: Classification of Germline Variants in Hereditary Breast -Ovarian Cancer Genes: How to Specify Types & Weight of Evidence
  • Date: 15 October
  • VHIO Host: Sara Gutiérrez-Enríquez, Senior Investigator, Hereditary Cancer Genetics Group

  • Speaker: Teresa Palomero, Associate Professor of Pathology & Cell Biology (in the Institute for Cancer Genetics), Columbia University Irving Medical Center, New York, USA
  • Talk title: Mechanisms of Transformation in Peripheral T-Cell Lymphomas
  • Date: 11 November
  • VHIO Host: Marta Crespo, Translational Research Coordinator, Experimental Hematology Group

  • Speaker: Jesús Bañales, Investigator Miguel Servet II and CIBEREHD (ISCIII), Ikerbasque Research Professor & Head, Liver Diseases Group, Biodonostia Health Research Institute – Donostia University Hospital, San Sebastian, Spain.
  • Talk title: The Role of Protein NEDDylation in the Pathogenesis of Cholangiocarcinoma: Novel Therapeutic Opportunities
  • Date: 26 November
  • VHIO Host: Sandra Peiró, PI, Chromatin Dynamics in Cancer Group

  • Speakers: Evon Poon, Senior Scientist, Institute of Cancer Research (ICR), and John Anderson, Professor, Experimental Pediatric Oncology, University College London (UCL) Great Ormond St. Institute of Child Health, London, UK
  • Talk title: Combined Small Molecular & Immune Strategies to Target MYC- Driven Pediatric Cancers
  • Date: 03 December
  • VHIO Host: Laura Soucek, PI, Models of Cancer Therapies Group

  • Speaker: Íñigo Martincorena, Group Leader, Sanger Institute, Cambridge, UK
  • Talk title: Somatic Mutations & Clonal Expansions in Normal Tissues
  • Date: 10 December
  • VHIO Host: César Serrano, PI, Sarcoma Translational Research Group

www.vhio.net/events/scientific-seminar-series


Our Benchstorming Co-Chairs (left to riaght): Chiara Bellio, Associate Researcher of our Tumor Biomarkers Group (PI: Josep Villanueva), Sara Simonetti, Attending Physician of VHIO’s Molecular Oncology Group (PI: Paolo Nuciforo), and Tian Tian, Senior Scientist of our Chromatin Dynamics in Cancer Group (PI: Sandra Peiró).

Established in 2016, our annual series of Benchstoming Seminars represent an excellent educational opportunity for junior faculty at VHIO to both present and exchange on and around their respective research interests across VHIO’s various research programs.

Not only do our young researchers learn more about their other colleagues and research lines currently underway, they can also express their ideas surrounding a given topic presented at each seminar; the specially crafted informal format favors free thought, flow, and interaction between the speakers and participants.

Reflective of VHIO’s purely translational and multidisciplinary research model, 2021 marked the launch of additional seminars that counted on the participation and expertise of our Clinical Investigators and Medical Oncologists.

In 2021, 18 Benchstorming Sessions took place, mostly remotely online due to the COVID-19 pandemic. Each invited VHIO investigator(s) discussed and ‘benchstormed’ their respective research areas. www.vhio.net/events/benchstorming-seminars


Ad-hoc courses, workshops, perceptorships & observerships

1.EvolutIOn. Una nueva visión en el tratamiento del cáncer (7ª edición), 01 February. Coordinators: Enriqueta Felip, PI, VHIO’s Thoracic Tumors & Head and Neck Cancer Group, Joan Carles, PI, VHIO’s Genitourinary, CNS Tumors, Sarcoma & Cancer of Uknown Primary Site, and Eva Muñoz, Clinical Investigator & Medical Oncologist, VHIO’s Breast Cancer and Melanoma Group. 2. Preceptorship en Genética del Cáncer Hereditario, 09 - 10 June. Coordinator: Judith Balmaña, PI, VHIO’s Hereditary Cancer Genetics Group. 3. Preceptorship en Cáncer de Ovario, October - December. Coordinator: Ana Oaknin, PI, VHIO’s Gynecological Malignancies Group. 4. Manejo del Cáncer de Mama en la era COVID-19, 14 October. Coordinator: Juan Aguilar-Company, Internal Medicine & Infectious Diseases Specialist, Vall d’Hebron University Hospital’s Medical Oncology Department (headed by Josep Tabernero). 5.Gastrointestinal Cancer and Neuroendocrine Malignancies Program, 11 November. Coordinators: Josep Tabernero, VHIO’s Director, and Teresa Macarulla, PI, VHIO’s Gastrointestinal & Endocrine Tumors Group. 6. Lung Cancer Program, 02-03 December. Coordinator: Enriqueta Felip, PI, VHIO’s Thoracic Tumors & Head and Neck Cancer Group.

Based on specific lines and research areas that continue to position VHIO as a leading international reference, we share our expertise, learn from eminent guest speakers, discuss and debate our latest findings through the organization of VHIO ad-hoc courses and workshops.

Exchanging latest discovery in cancer science and medicine, VHIO organized 18 Courses, Workshops, Observerships and Perceptorships in 2021. Naturally, due to the COVID-19 pandemic, the majority of these were hosted and conducted virtually, online.

In addition to these educational opportunities, we have organized and streamed several expert talks and presentations, as well as produced, published and disseminated various on-demand webinars covering a broad range of topics and tumor types.

www.vhio.net/events/workshops-courses


VHIO’s patient engagement events, fundraising, and public outreach activities

VHIO supports and organizes activities to increase public interest in cancer research and promote the important advances reported by our scientists and clinical investigators. These efforts are aimed at patients, youngsters and non-specialized adult audiences to enrich scientific culture as well as promote science as a stimulating career path for young people – the future of our research.

Importantly, some of these initiatives have resulted in considerable funding for research at VHIO, as documented in this section of our scientific report. We will continue to seek out, lead and participate in all these precious initiatives and launch new ones based on identified opportunities.

In addition to VHIO’s comprehensive lay media program, the invited participation of our researchers and clinical investigators across a broad range of communication channels, and campaigns tailored to our social media platforms and respective target audiences, VHIO led and/or participated in several public outreach events, programs and fundraising initiatives in 2021.

Due to the COVID-19 pandemic, many of our planned activities had to be cancelled or postponed. The majority of those that could go ahead were either conducted virtually, or carried out in strict compliance with the stipulated social distancing rules and required safety measures.

Illustrative of these efforts, we take this opportunity to mention just a few of the many highlights in 2021:

Connecting and conversing with cancer patients outside of the clinic

At VHIO we are committed to organizing and promoting educational programs especially tailored to those who matter most; our cherished patients.

Providing opportunity for debate and exchange among patients, their families and loved ones, and connecting them with our physician-scientists, cancer researchers, and other professionals in oncology, we co-organize an annual series of breast cancer workshops:

7th edition of our annual breast cancer workshops (October 2021 – June 2021)
HUVH-VHIO’s annual breast cancer workshops for our cancer patients, their families and friends, as well as the general public.

Launched in 2015, these workshops are coordinated by Marta Capelan, a Medical Oncologist and Clinical Investigator of VHIO’s Breast Cancer Group, directed by Cristina Saura, and organized in collaboration with the Vall d’Hebron University Hospital’s (HUVH) Breast Cancer Unit, also led by Cristina Saura, and other expert teams across the Vall d’Hebron Barcelona Hospital Campus.

This year, these workshops were supported by Pfizer and icrom Clinical Research Office Management, in collaboration with the Asociación Endavant Chic@s. Due to the safety issues posed by the COVID-19 pandemic these events took place online.


In 2021, we launched a new monthly series of live online sessions covering several tumor types, that have been especially crafted for cancer patients and non-specialized audiences #VHIOATuLado.

Inaugurating this new series of special sessions, were VHIO’s Enriqueta Felip, Principal Investigator of our Thoracic Tumors & Head and Neck Cancer Group, and Head of the Thoracic Cancer Unit at the Vall d’Hebron University Hospital (HUVH), and Alberto Jauregui, Head of the Thoracic Surgery Service at Vall d’Hebron. Discussing various aspects relating to the diagnosis of lung cancer, they presented on the recent developments in this field, including the latest advances in patient treatment and care.

Throughout each of these dedicated sessions, also including experts in preclinical, translational and clinical cancer research, participants are invited to post their comments and questions online to actively contribute and engage in the various topics that are discussed and debated.

For a full listing of these educational opportunities in 2021, we invite you to visit the extended version of this scientific report online at: http://memorias.vhio.net/2021 (select ‘Education & Training’).

Public fundraising in support of cancer research

Pau Donés and Jarabe Contra el Cáncer

Left to right: One of the promotional posters for Pau’s sell-out fundraising rock concerts, and Pau on stage with VHIO’s Elena Élez.

We remain deeply saddened by the passing of Pau Donés, singer, songwriter, guitarist and leader of the renowned Spanish rock group Jarabe de Palo, who, having been diagnosed with colorectal cancer in 2015, succumbed to his disease on 09 June 2020.

Receiving treatment at our Vall d’Hebron University Hospital (HUVH), and cared for by our medical teams and specialists, particularly Elena Élez, Medical Oncologist and Clinical Investigator of our Gastrointestinal & Endocrine Tumors Group, he was a treasured patient, friend, and an ardent believer in the importance of research against cancer.

To raise funds for research at VHIO, he not only organized various Jarabe Contra el Cáncer sell-out concerts with his band and several other renowned musicians, but also spoke out to raise awareness on and around cancer. As Pau prepared for his death, he contacted journalist Jordi Évole to discuss his own final fundraising initiative against cancer. Eso que tú me das –the title of one of his very last songs recorded with his band- was to be the title of the documentary and very final interview, which broadcast in cinemas across Spain, following his passing.

Directed by Ramón Lara and Jordi Évole, and produced by Producciones del Barrio y Atresmedia, all proceeds were donated to support several research projects at VHIO.

Vivir es Urgente 2021

Pictured: the presentation of the first cheque for 350.000€ just one month after the campaign launched in June 2021, with Pau’s brother Marc Donés, Marta Cardona, Director of the Fundación Cris Contra el Cáncer, Jorge Martínez and José Maria Piera from the Help! Buenas Ideas network, along with VHIO’s Director, Josep Tabernero, Alejandro Piris, Elena Élez, Raquel Lopez-Perez, and Joaquin Mateo, whose research will be supported by this funding.
The Fundación CRIS contra el Cáncer, Jarabe Contra el Cáncer, Pau’s family including his brother Marc Donés, in collaboration with the Help! Buenas Ideas network, launched a new fundraising initiative in 2021: La Camiseta Pau (Pau’s T-shirt). Marking the 1st anniversary of his passing, these T-shirts went on sale in June to raise funds for research at VHIO. Within just one month, this initiative raised an incredible 350.000€, and by the close of the campaign in September, succeeded in raising a total of 524.581€.

This T-shirt, with the slogan Vivir es urgente (Life is urgent), was designed by Pau Donés and worn by him at another of his fundraising concerts that took place in Mexico City, October 2017. These three words became a mantra during his final years.

Pau Donés, you will never be forgotten.


Left to right: Cristina Saura, Inés Gasén, and Meritxell Bellet.

El Paseíco de la Mama (loosely translated as strolling for breast cancer) began to take shape when Inés Gasén was diagnosed with breast cancer during her pregnancy – not only naturally provoking fear and uncertainty for her and her family, but also raising many questions and doubts concerning the health and the future ahead for her baby.

Triggering a call to action in her mother in-law, Elaine, and driven by the need to bring a positive out of the then challenging times, she decided to organize an annual sponsored walk to raise funds aimed at advancing insights into breast cancer. Rallying support among their family and circle of friends and acquaintances, Elaine and her two daughters Pili and Susan, and Inés, founded El Paseíco de la Mama in 2011.

From the very outset, El Paseíco de la Mama has been a tremendous supporter of research directed by Cristina Saura, Principal Investigator of our Breast Cancer Group and Head of the Vall d’Hebron University Hospital’s Breast Cancer Unit, and continues to gain momentum year in, year out, with an increasing number of participants, donations and personal pledges.

While the 2020 sponsored 7.5 km walk along Zaragoza’s canal had to be held later on that year due to the COVID-19 pandemic, this did not deter the fundraising efforts. This year, Inés Gasén presented Cristina Saura and Meritxell Bellet with a cheque for 38.485€. This support will fuel research aimed at reliably measuring blood estradiol in premenopausal women with breast cancer undergoing hormonal treatment, led by Meritxell Bellet.


Left to right: Marta Capelan, Cristina Saura, Luisa Vázquez – President of the Asociación Endavant Chic@s, and Judith Balmaña.

Asociación Endavant Chic@s organizes several fundraising sports tournaments and other initiatives throughout the year. As a result of these efforts, it succeeded in raising 11.405,34€. This donation, presented to VHIO’s Cristina Saura, Judith Balmaña, and Marta Capelan by the Association’s President, Luisa Vázquez in 2021, will fund essential research aimed at improving outcomes and the quality of life of breast cancer patients at the Vall d’Hebron University Hospital’s Breast Cancer Unit, headed by Cristina Saura.

Specifically, this donation will support a project led by Judith Balmaña, Principal Investigator of our Hereditary Cancer Genetics Group, aimed at better calculating the risk of developing breast cancer using predictive models toward more precisely anticipating and preventing disease in individual patients.

In addition, it will also co-fund research into the benefits of yoga in alleviating fatigue associated with breast cancer. A randomized study will include a group of patients undergoing neoadjuvant chemotherapy treatment who will participate in two weekly yoga classes online due to the issues posed by the COVID-19 pandemic, and a control group. This research is also supported by the aforementioned Paseíco de la Mama.


The not-for-profit Em dones força association presents VHIO’s Cristina Saura and Meritxell Bellet with 10.000€ to advance breast cancer research and the treatment and care of patients.

Em dones força, created by a group of friends in Riudoms, Tarragona (Catalonia) to raise funds for breast cancer research through a variety of activities, presented VHIO’s Cristina Saura, Principal Investigator of our Breast Cancer Group, and Meritxell Bellet, a Clinical Investigator and Medical Oncologist of Cristina's group, with a cheque for 10.000€ as a result of their fundraising efforts.

Meritxell Bellet was Elvira Mas’ oncologist. Elvira was a co-founder of and President of Em dones força, who sadly recently passed away from breast cancer. The official presentation of this important donation took place at VHIO’s CELLEX Building, and paid tribute to Elvira and her legacy. Fifty people, including her husband, children, family members, friends and neighbors in Riudoms, all of whom form part of Em dones força, attended this special event.

Funding will support Meritxell Bellet’s project entitled: Recruiting ERβ in the fight against triple negative breast cancer (TNBC).This research could potentially provide new treatment avenues for these patients.


Pañuelo Solidario’: solidarity scarves for cancer research

The launch of the 4th ‘Pañuelo Solidario’ 2021 campaign at Vall d’Hebron.

‘Pañuelo Solidario’ is a fundraising campaign driven by the Vall d’Hebron University Hospital (HUVH), in collaboration with the lifestyle store Natura that produces and distributes these solidarity scarves in its shops and online. All proceeds will be donated to support cancer research carried out by two predoctoral researchers. They are Alejandra Cano of VHIO’s Breast Cancer Group, and Carina Masferrer, the Gynecological Biomedical Research Group at the Vall d’Hebron Institute of Research (VHIR).

Established in 2017 by the campaign’s ambassador, Judit Mascó, and designed each year by artist Clàudia Valsells, this fundraising initiative seeks to improve the treatment and wellbeing of women suffering with breast cancer and gynecological cancers. Timed to coincide with International Women’s Day, held annually on 08 March, the official launch of this year’s campaign took place at Vall d’Hebron in strict compliance with all the COVID-19 pandemic safety and control measures.

Alejandra Cano’s research focuses on STEPS – therapeutic support for cancer survivors. This project is dedicated to providing more resources and psychological support for patients after their diagnosis and post-treatment to alleviate anxiety and emotional stress, as well as tools to facilitate their reincorporation into daily life, both at the personal and professional levels.

Carina Masferrer’s research centers on developing new therapeutic strategies for the more effective treatment of endometrial cancer. She is currently assessing the efficacy of a targeted therapy with a small-molecule, ABTL0812, in combination with immunotherapy. This approach could open up new treatment avenues for patients, particularly for those with aggressive disease.


On the occasion of the Associació Solidària Sosciathlon’s 6th annual public fundraiser, VHIO’s Ramon Amat and Caterina Carbonell were presented with a donation of 10.000€ in support of research carried out by VHIO’s Thoracic Tumors & Head and Neck Cancer Group.

Celebrating its 6th annual public fundraiser, that took place in La Pineda, Vila-seca (Tarragona, Catalonia), the Associació Solidària Sosciathlon (Solidarity Association Sosciathlon) raised a total of 20.000€, that was evenly split between VHIO and the ENACH.ORG distrofia neuroaxonal infantil (ENACH. ORG infantile neuroaxonal dystrophy). This year’s sports event attracted some 1,000 participants and secured funding through sponsorship, event registrations, donations, and merchandise sales.

This donation will support research carried out by Enriqueta Felip’s Thoracic Tumors & Head and Neck Cancer Group that focuses on disease prevention, early detection and staging of these tumor types toward improving clinical outcomes. On behalf of Enriqueta’s team, Ramon Amat, Associate Researcher, and Caterina Carbonell, Post-Doctoral Fellow of her group, were presented with a donation of 10.000€ that will fuel essential research aimed at improving outcomes for patients suffering from thoracic malignancies and head and neck tumors.

Established in 2014, the Associació Solidària Sosciathlon fosters value-based solidarity, volunteering, help and commitment, and donates the proceeds from their annual events between two different entities, while promoting health and culture through sport.


Advancing insights into sarcomas: SarcModel (ing)

Carlota Coloma and her family have this year donated 15.000€ to support translational research into sarcomas led by VHIO’s César Serrano.

Sarcoma is a very rare tumor type; representing between 1-2% of all cancers. It is also a highly complex disease with more than 70 subtypes; each with a different biological makeup and clinical behavior. For these reasons, VHIO’s César Serrano, who leads our Translational Sarcoma Research Group, initiated the SarcModel project that focuses on advancing cancer modelling against this disease.

In support of these efforts, Carlota Coloma, Director of the production company 15LFilms and alma mater of the documentary Backstage. Hablemos de un sarcoma (Backstage. Let’s talk about sarcoma), set about raising funds. Alongside her family, and with the support received from various sponsors, this documentary was produced in honor of her mother who passed away from sarcoma, in order to help other families going through the same experience. It also superbly documents how researchers and oncologists work together to seek out more effective treatments against this disease.

Through the Migranodearena crowdfunding platform, they succeeded in raising 15.000€ to help advance sarcoma research at VHIO. Specifically, this donation will spur César’s Group’s SarcModel project that ultimately aims to extend the promise of precision medicine in oncology to sarcoma patients.


We also take this opportunity to gratefully thank the many other entities, organizations and individuals, including our cherished patients, who also dedicate their precious time, energy and efforts in supporting our public, national outreach program as well as raising funds for our research through individual as well as crowdfunding activities.


Public outreach and engagement

World Cancer Day (WCD), 04 February, is led by its founding and organizational body, the Union for International Cancer Control (UICC). To mark the occasion in 2021, VHIO’s Director, Josep Tabernero, Enriqueta Felip (PI: Thoracic Tumors & Head and Neck Cancer Group), Elena Garralda (PI: VHIO’s Early Clinical Drug Development Group), and Director of our Research Unit for Molecular Cancer Therapy of Cancer – UITM, CaixaResearch), Ana Vivancos (PI: Cancer Genomics Group), and Alena Gros (PI, Tumor Immunology & Immunotherapy Group), were among other leading experts in oncology across the Vall d’Hebron Barcelona Hospital Campus, who were invited as panelists and speakers.

Including the participation of cancer patients, and aimed at the general public at large, this special event addressed key topics including the latest advancements in oncology, cancer prevention, and important aspects regarding the wellbeing and care of people suffering from this disease.

VHIO investigators joined together with other researchers and healthcare professionals in oncology at Vall d’Hebron to mark World Cancer Day 2021.

World Cancer Day 2021 not only celebrated its 21st birthday but also the final year of its ‘I Am and I Will’ 3-year global campaign. As importantly, it also recognized the extraordinary efforts of hospitals, cancer organizations, research institutes, cancer care professionals and providers, volunteers, advocates and individuals around the world who rapidly responded to the myriad challenges posed by the COVID-19 pandemic.

It praised the valiant actions of all stakeholders in oncology, including funding bodies, government agencies, regulatory authorities, and the pharmaceutical industry who continued to work together in maintaining progress in cancer research, treatment and care. Capturing just some of these amazing endeavors, the UICC launched a dedicated web page: Adaptations and innovations in cancer care through COVID-19 and beyond, that encapsulated the bravery and achievements of people living with cancer and their families, as well as the nurses, doctors, researchers, advocates and others who care for them throughout the COVID-19 crisis.


Coinciding with the International Day of Women and Girls in Science, celebrated annually on 11 February, several of our researchers participated in two different programs. The first, CONÓCELAS, was organized by the Asociación Española de Investigación sobre el Cáncer – ASEICA (Spanish Association of Cancer Research), in collaboration with the Red de Asociaciones de Investigadores y Científicos Españoles en el Exterior - RAICEX (Network of Associations for Spanish Researchers and Scientists Abroad), and the Ciencia es Femenino (Science is Feminine) organization in Galicia.

Taking place virtually this year due to the COVID-19 pandemic, the main objective of this event is to give visibility to the important contributions made by female researchers in combating cancer. CONÓCELAS, also supported by VHIO’s María Abad (PI: Cellular Plasticity & Cancer Group) as a driving force, connected around 6,500 students throughout Spain with 150 investigators to discover more about the work of today’s female rising stars in cancer research and oncology.

The second, #100tífiques, is a joint initiative of the Fundació Catalana per a la Recerca i la Innovació – FCRI (Catalan Foundation for Research and Innovation), and the Barcelona Institute of Science and Technology (BIST), in collaboration with the Departament d’Educació de la Generalitat de Catalunya (Deparment of Education, the Government of Catalonia).

The main goals of #100tífiques are to promote the relevance and role of women in science and technology, and foster collaboration between scientists from academia and enterprise. It also seeks to achieve a more direct and reciprocal relationship between science and society.

Now in its 3rd edition, 2021 counted on the participation of around 100 women in science (pre-doctoral students, postdocs, group leaders and directors of research from both the public and private sectors), including 13 VHIO scientists, who gave virtual talks to primary and secondary school students throughout Catalunya.


Movember, celebrated globally throughout the month of November, was established back in 2003. This public awareness movement has since gathered tremendous momentum worldwide; having financed over 1,250 projects in men’s health globally.

Vall d’Hebron teams once again joined the Movember movement against prostate cancer in 2021.

For another year, physicians, investigators and healthcare professionals at the Vall d’Hebron University Hospital’s – HUVH Urology Service, Vall d’Hebron Institute of Research (VHIR), and VHIO’s Prostate Cancer Translational Research Group (PI: Joaquin Mateo), joined together to support this campaign at the national level through the Fundación Movember, and the #MovemberTeam. By the year 2030, the Movember aims to reduce the number of men who die prematurely from prostate cancer through preventable causes by 25%.

This year, their official MOVEMBERVHIO/HUVH funding page invited donations, and encouraged the sporting of moustaches to mark the movement and promote via social media platforms #Movember2021, among other public awareness actions and activities.


One of the many Movember-supported projects includes the IRONMAN Registry, for which VHIO serves as the central laboratory in Spain, led by Joaquin Mateo, Principal Investigator of our Prostate Cancer Translational Research Group. IRONMAN is an international, population-based registry that will include 5000 men with advanced prostate cancer across ten countries, 500 of whom will be from Spain. It seeks to advance insights into the clinical outcomes associated with the management of this disease as well as better understand its biological and clinical diversity.

Nationally, this project is implemented by the Fundación Movember and co-funded by one of VHIO’s Patrons and Institutional Supporters, Fundación FERO. Counting on the expertise of investigators at VHIO and colleagues at the Spanish National Cancer Research Center – CNIO (Madrid), who coordinate this program, along with a network of global data centers and their participating sites, this project represents an important step forward in advancing precision medicine against advanced prostate cancer.


Nit Europea de la Recerca

VHIO’s Sandra Peiró presenting on epigenetics and cancer.

The Nit Europea de la Recerca (European Night of Research) is celebrated annually in more than 300 cities across 30 countries throughout Europe, including Barcelona. This event was established to enable members of the public to meet researchers, learn about their respective scientific disciplines, research lines and activities.

In 2021, this scientific soirée counted on the participation of a trio of VHIO investigators. Hosted by venues including the CosmoCaixa Barcelona, the ”la Caixa” Foundation Sandra Peiró, Principal Investigator of our Chormatin Dynamics in Cancer Group, talked about epigenetics and its role in cancer.

Carmen Escudero, a Graduate Student of Sandra’s group, and Joana Domènech, a Graduate Student of our Hereditary Cancer Genetics Group, headed by Judith Balmaña, led a workshop on genetic mutations in cancer aimed at younger audiences. Using pieces of LEGO® they superbly simplified a complex topic.


La Festa de la Ciència 2021

Left to right: VHIO’s Carmen Escudero was invited to explain genetic mutations in cancer using pieces of LEGO®, and Marta Ligero presented on the promise of AI in advancing precision medicine in oncology.

Promoted by the Ajuntament de Barcelona (Barcelona City Council), 2021 celebrated the 14th annual edition of the Festa de la Ciència (Celebration of Science) that took place in person adhering to all the social distancing rules and restrictions posed by the COVID-19 pandemic. This public event was established as an educational forum to learn about, consider and update on the many challenges that are being tackled through research of excellence.

Universities, research centers, including VHIO, other scientific institutions and companies, and experts in scientific communication, joined together to devise a stimulating and informative program of matched excellence in 2021. The agenda included over 120 different talks, presentations and activities for people of all ages.

Regarding VHIO’s contributions to this annual celebration of science, Carmen Escudero, a Graduate Student of our Chromatin Dynamics in Cancer Group led by Sandra Peiró, gave a talk on genetic mutations in cancer. Using pieces of LEGO®, she was able to creatively explain how faulty genes lead to cancer.

Marta Ligero, a PhD Student of VHIO’s Radiomics Group, directed by Raque Perez-Lopez, gave a mini talk on Artificial Intelligence (AI), to decipher the secrets of medical images. Throughout her talk, Marta explained how AI can advance crucial insights into cancer, representing a step forward in precision medicine in oncology.

Several other researchers and experts from across the Vall d’Hebron Barcelona Hospital Campus also participated in this event including Paula Galvá from the Vall d’Hebron University Hospital (HUVH), who gave a talk on the importance of telemedicine in the COVID-19 era and how it has revolutionized certain aspects of healthcare delivery.

Open house: Vall d’Hebron’s Science and Innovation Week

Welcoming visitors to discover more about VHIO’s suite of Core Technologies.

In 2021 our Vall d’Hebron Barcelona Hospital Campus launched its first Science and Innovation Week, 15-19 November, that provided the general public with a great opportunity to learn more about cutting-edge platforms, tools and techniques on-campus that are shaping the future of healthcare, including augmented and virtual reality in healthcare, robotics, simulation, and 3D technologies. Including activities for faculty at Vall d’Hebron and other institutions, the week’s educational program also offered an exciting range of events aimed at younger audiences.

Forming part of Vall d’Hebron’s strategic plan to promote its innovation, driven and developed in-house, this event was also established to give researchers, clinical investigators, technicians and healthcare professionals who spur these stunning advances in medical technologies greater visibility in society.

The inaugural program also included five roundtable sessions covering healthcare and telemedicine in the digital age, as well as a series of presentations dedicated to spin-offs and start-ups at Vall d’Hebron. These included talks by VHIO’s Joan Seoane and Laura Soucek, Co-Directors of our Preclinical and Translational Research Program -both ICREA Research Professors- who discussed the value of technology transfer in society and the promise of these companies in improving outcomes for patients. Illustrative of these efforts, they each introduced participants to their respective VHIO-born spin-offs, Mosaic Biomedicals, and Peoptomyc.


This dedicated VHIO educational program (established back in 2017), welcomes under-twelves from various local primary schools to meet our faculty, tour our laboratories and learn more about cancer biology and research.

The main objectives of our Schools and Science outreach program are to teach young and inquisitive minds about the importance of cancer research, and hopefully inspire some of them to ultimately become the next generation of cancer scientists.

During their half-day visits our young visitors participate in junior masterclasses and hands-on activities to explain the origins and development of cancer, led and supervised by VHIO faculty. Unfortunately, due to the safety issues posed by the COVID-19 pandemic, we had to postpone our 2021 program of activities. In view of the excellent feedback that we receive from students and teachers alike, we will continue to open our doors to all primary schools who wish to participate in this program, with dates already in the diary for 2022 – pandemic restrictions permitting.


VHIO’s social media channels & platforms

In addition to VHIO’s comprehensive lay media program and the invited participation and presence of our researchers and clinical investigators across a broad range of communication channels, we continue to expand our outreach through news announcements, campaigns, images, and videos tailored to our social media platforms and respective target audiences.

To discover what we are excited about, our latest news, and other developments that are catching our attention elsewhere, we invite you to follow us, and join in on our ‘conversation’ today: