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Foreword by VHIO’s Director

VHIO in 2019: tick tock toward 2025

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

To mark the 25th anniversary of Nature Medicine in 2019, the journal’s editorial team invited me and ten other experts in biomedicine to contribute to a special news feature by answering the question: What will shape the next 25 years of medical research? (1). As part of my response, I began by arguing that sweeping statements would be imprudent. Indeed, who would have predicted that the future of biomedicine, research and the treatment and care of patients suffering from serious diseases such as cancer, would be compromised by the rapid and global explosion of COVID-19?

I strongly believe in joining forces, nurturing and developing partnerships, and exchanging data to overcome the many challenges that hamper our efforts in solving cancer sooner. Alongside like-minded experts in oncology, we have forged numerous international consortia and multi-center studies that continue to drive spectacular advances against this disease. As importantly, we have learned from each other’s experiences, successes and failures in order to avoid costly duplication and accelerate progress.

As this report goes to press, an article in The Lancet (2) caught my attention. Sadly, the piece sheds a glaring light on the lack of collaboration and synergy between nations in tackling the COVID-19 catastrophe. Not only has this pandemic destroyed the foundations for protecting and advancing health, but also it is threatening the aims set out in the Millennium Development Goals and (since 2016) the Sustainable Development Goals. Simply put, the clock is ticking.

This brings me back to the number 25. It is in fact the focus of this year’s Scientific Report cover; a VHIO time bar towards 2025.

Here’s why:
The year 2025 is the deadline to attain the World Health Organization’s (WHO) nine voluntary global targets for noncommunicable diseases (NCDs) and mental health. Target 1 promises a 25% relative reduction in overall mortality from cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases. Progress in implementing the NCD Global Action plan is tracked by WHO’s Global monitoring framework on NCDs in order to monitor and report on the attainment of its nine global targets for NCDs by 2025. While COVID-19 is threatening our collective efforts to achieve this ambition in cancer, I believe that together – along with the vital funding and necessary support networks firmly in place -- achieving this target might be within reach.

One of the major European funding programs, Horizon Europe, was announced in 2019 and succeeds the European Commission’s Horizon 2020 funding program for research for research and innovation. Within Horizon Europe’s framework, five key research and innovation missions have been identified to increase the effectiveness of funding by pursuing clearly defined targets, ‘Missions’, including cancer. The Cancer Board, chaired by Walter Ricciardi (Rome, Italy), is flanked by its respective Assembly, on which I am truly honored to serve. The Board and Assembly Members will collectively seek to deliver on Mission’s goals. They are: to ensure that more people live without cancer, more cancer patients are diagnosed earlier, suffer less and have a better quality of life after treatment.

But it’s not just a matter of strengthening and securing vital funding for cancer research of excellence. To deliver on these aforementioned ambitions, we must also seek to address many other serious concerns. As an example, The European Society for Medical Oncology (ESMO) -- for which I have had the privilege to serve as President throughout the 2018-2019 term -- has taken the lead in driving EU level action to tackle the serious shortages of essential cancer medicines. These identified shortages obviously have a direct impact on patient care across Europe. To ensure that this issue remains a top priority on the EU policy agenda, ESMO collaborated with the European Parliament to organize a cross-partisan event entitled Shortages of Inexpensive, Essential Medicines: Calling for Tangible Political Commitments in the EU, 09 April, Brussels (Belgium).

During my ESMO Presidency, The Economist Intelligence Unit and ESMO prepared a series of reports on medicine shortages in five countries – Germany, Bulgaria, Romania, Belgium, and Finland. The resulting country profiles show that unfortunately there is a lack of data on the magnitude of the issue and that European and international collaborations are key to facilitate the exchange of products in short supply. To further expose this growing public health emergency, which requires concerted and collaborative action at the EU level, members of ESMO’s European Policy Committee co-authored a commentary (3) to report on these shortages and signal next steps to tackle this alarming reality.

In this context, I am delighted to announce that the role of ESMO’s Magnitude of Clinical Benefit Scale (ESMO-MCBS) as a screening tool to identify cancer treatments that have potential therapeutic value (warranting full evaluation for the WHO’s Essential Medicines List) was acknowledged by WHO’s Expert Committee on Selection and Use of Medicines in the 22nd WHO Expert Committee on the 2019 Selection and Use of Medicines Report. Specifically, the Committee stated that ‘all new EML cancer medicines, in general, should have a score on the ESMO-MCBS of A or B in the curative setting and of 4 or 5 in the non-curative setting. These scores would support a medicine being evaluated by the Expert Committee for inclusion in the EML through a full application’.

The ESMO-MCBS major value-based framework, launched in 2015, continues to undergo finely-tuning in order to incorporate additional features and criteria. Under constant internal peer review, it has also recently been enriched with newly designed forms, a factsheet and booklet to facilitate the understanding of criteria, grading and outcomes. These resources should help to clarify certain misconceptions reported in the literature this year – addressed by members of ESMO’s Cancer Medicines Committee (4).

Importantly, ESMO is not alone in these policy-orientated efforts. the European Association for Cancer Research (EACR), American Society of Clinical Oncology (ASCO), and the American Association for Cancer Research (AACR) – as well as many others – are all working shoulder to shoulder with other specialties, policy makers, as well as patient advocacy groups across the globe, to overcome the obstacles thwarting the optimal treatment and care for all cancer patients. One patient is one too many.

At VHIO, we are dedicated to advancing translational cancer science and medicine toward significantly improving outcomes for our patients. As VHIO’s Director, I’m honored to highlight some of the many important contributions made by our multidisciplinary research teams in 2019, often in partnership with colleagues across the globe as well as leading European and international consortia. For an additional pick of papers please refer to From the Directors.

Impactful cancer science and medicine at VHIO

In 2019, VHIO researchers and clinical scientists published an impressive 333 scientific articles in leading journals as corresponding, senior, or co-authors. Many of these were published in the world’s most prestigious scientific and medical journals.

Here is just a small sample of our studies that deservedly made headlines in 2019:

Driving transformative research closer to the clinic

Novel agent reactivates an immune call by LIF blockade

Joan Seoane, Co-Program Director of Preclinical and Translational Research at VHIO and ICREA Research Professor.

Building on previous VHIO research pioneered by our Gene Expression & Cancer Group, results from a study(5), led by Joan Seoane, Co-Program Director of Preclinical and Translational Research, and ICREA Research Professor, have shown that the blockade of the multi-functional cytokine LIF induces tumor-infiltrating T cells to target and eliminate cancer.

Developed by VHIO, novel agent MSC-1 inhibits LIF and has now been shown to have a dual mechanism of action. First, in tumors expressing high levels of LIF, this protein promotes the proliferation of cancer stem cells. LIF blockade eliminates these tumor-initiating stem cells, putting the brakes on metastatic cell spread and cancer recurrence. Additionally, elevated LIF expression disables the anti-tumor alarm system and stops the immune system from thwarting cancer’s plans. Blocking LIF reactivates the alarm to call an anti-tumoral immune response.

This research, carried out in collaboration with other VHIO groups and departments at the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, has now shown that LIF inhibits the CXCL9 gene, which acts as a signal to lure immune system T cells. LIF blockade induces these immune system soldiers to invade, attack and destroy tumors. The study also showed that combining LIF inhibition with anti-PD1 therapy delivers powerful blows against cancer. Once the T cells infiltrate the tumors, they are activated by anti-PD1 immunotherapy. In animal models the pairing of both agents not only halted tumor growth but also, in some cases, made tumors disappear.

Pushing Myc inhibition closer to the clinic

Laura Soucek, PI of VHIO's Mouse Models of Cancer Therapies Group (right), ICREA Research Professor, and Co-Founder of Peptomyc S.L.

Another translational VHIO study from 2019 (6) represents an important forward step in driving the Omomyc mini-protein closer to the clinic. Findings led by Marie-Eve Beaulieu, CSO and co-founder of VHIO-born spin-off Peptomyc, directed by Laura Soucek, PI of our Mouse Models of Cancer Therapies Group, ICREA Research Professor and Co-Founder and CEO of Peptomyc, provided evidence for Omomyc as the first efficient and tolerable MYC inhibitor for the treatment of non-small cell lung cancer (NSCLC).

For the first time, the authors establish that Omomyc can be purified and administered in vivo, rapidly reaching the tumor site. Results showed that it successfully inhibits its target, leads to reduced tumor grade and promotes regression of existing disease. Thanks to Marie-Eve’s particular expertise in peptide design and production, the team succeeded in scaling up the purification process of the mini-protein and re-assessing its therapeutic activity via intravenous administration. Its systemic delivery unleashes the anti-cancer potential of Omomyc and extends its application to the treatment of other tumors and metastases.

Omomyc may attack tumors not only through the blocking of proliferation and the induction of apoptosis, but also by triggering an immune response. The inhibitor can alter the profile of molecules released by cancer to trick the immune system, and may increase the infiltration of T lymphocytes into the tumor. This is relevant as immunotherapy is showing increasing promise in the treatment of several tumor types, but not all. The potential capacity of Omomyc to recruit immune cells at the tumor site, ‘spoilered’ in the study, indicates that it could also synergize and resensitize resistant tumors to immune-based therapies.

The promise of novel chimeric antigen receptor (CAR) T-cell immunotherapy

Co-Program Director of VHIO’s Preclinical and Translational Research and ICREA Research Professor.

In 2019, our Growth Factors Group, led by Joaquin Arribas, Co-Program Director of Preclinical & Translational Research at VHIO and ICREA Research Professor, initiated a new line of research focused on generating novel chimeric antigen receptors (CARs), as a strategy to use the immune system of patients to eradicate tumors. This approach has been enabled by the insights they previously gained by developing and characterizing bispecific antibodies. Specifically, these CARs are directed against the p95HER2 protein which is only found in some breast and gastric tumors, though completely absent in normal tissues.

Also this year, the group’s expanding platform of breast and pancreatic cancer patient-derived experimental models has led them to identify novel mechanisms of resistance to anti-cancer therapies (7), as well as seek out biomarkers of sensitivity to precision therapies (8), in collaboration with national and international groups.

Gauging response to target-directed therapies for the more precise stratification of patients

Héctor G. Palmer, Principal Investigator of VHIO’s Stem Cells & Cancer Group.

VHIO’s Stem Cells & Cancer Group, directed by Héctor G. Palmer, continues to make important progress in identifying molecular mechanisms conferring sensitivity or resistance to therapies in order to more precisely stratify patients for enrollment in clinical trials. Working in close collaboration with other VHIO groups and pharmaceutical companies, they seek to identify the molecular culprits that are responsible for the sensitivity or resistance to therapies blocking Wnt/beta-catenin, Notch, PI3K/AKT, EGFR/LGR5 or BRAF/MEK/ERK oncogenic signals.

As an example this year, and in collaboration with other Spanish investigators and VHIO teams including our Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla), Cancer Genomics (PI: Ana Vivancos), Molecular Oncology Group (PI: Paolo Nuciforo), Early Clinical Drug Development Group (PI: Elena Garralda), they have studied epigenetic EGFR gene repression and the conference of sensitivity to therapeutic BRAFV600E blockade in colon neuroendocrine carcinomas. Based on this published research (9), they are now designing new prescreening tests for a genetic-guided enrolment of patients in clinical trials. Importantly, their findings are helping to define new rational drug combinations to treat cancer patients with progressive disease.

Unmasking mechanisms of resistance in triple-negative breast cancer

Sandra Peiró, Principal Investigator, Chromatin Dynamics in Cancer Group.

One of the main challenges in more effectively treating triple-negative breast cancer (TNBC) is the acquisition of resistance to conventional chemotherapeutics. Research led by Sandra Peiró, Principal Investigator of our Chromatin Dynamics in Cancer Group, promises novel weaponry to more effectively combat cancer drug resistance in this particular tumor type.

This multi-center, Spanish study(10), also carried out in collaboration with VHIO’s Growth Factors (PI: Joaquin Arribas) and Molecular Oncology Groups (PI: Paolo Nuciforo) shows that, when compared to other breast cancer subtypes, the DNA of TNBC cells is much more compacted which renders it resistant to therapy. Results also indicate that chromatin decompaction could help to potentiate current therapies.

More specifically, the investigators identified oxidation of histone H3 as a key element in the induction of DNA compaction as well as discovered an association between compaction and resistance to anticancer agents. They also discovered that LOXL2 inhibition could prevent chromatin compaction from occurring. This is particularly relevant since this compaction seems to frequently occur in TNBC, which hinders therapies from accessing the nucleus of cancer cells. While this occurs in other types of breast cancer, they found that in those patients with the triple-negative subtype who show most resistance to conventional therapies, LOXL2 is present in high quantities, suggesting its role as a mechanism of resistance.

RAD51 as a biomarker in extending PARP inhibitors to additional tumor subtypes

Violeta Serra, Principal Investigator, Experimental Therapeutics Group.

Our Experimental Therapeutics Group, led by Violeta Serra, continues to mark important progress in gauging response to PARP Inhibitors (PARPi). Crucially, they have initiated the clinical validation of their RAD51predict test which is an immune-based assay performed on FFPE tumor sections. Reflective of its promise in better gauging efficacy of PARPi in individual patients and eventual implementation as a diagnostic test, these efforts have most recently been awarded by the ERA PerMed progam – an ERA-Net Cofund. This international project counts on the expertise of 32 partners from 23 countries, and is co-supported by the European Commission (Coordinator: Instituto de Salud Carlos III – ISCIII). The test is also being developed thanks to additional funding received this year from the CaixaImpulse Consolidate 2019 program.

Judith Balmaña, Principal Investigator, Hereditary Cancer Genetics Group.

Directed by Violeta Serra, and led by Alba Llop, post-doctoral fellow in our Experimental Therapeutics Group, the project not only centers on using RAD1 protein as a biomarker to help personalize cancer therapy, more precisely and rapidly predicting those patients who would be most likely to benefit from PARPi, better guide stratification in clinical trials, as well as extend PARPi for the treatment of additional tumor types beyond breast and ovarian cancers. This present research builds on the successes of several previous projects, including the previous PARPiPRED (which was also funded by CaixaImpulse), aimed at identifying clinical biomarkers of sensitivity to PARP inhibitors, and is spearhead by Violeta Serra’s Experimental Therapeutics Group, in collaboration with Judith Balmaña’s Hereditary Cancer Genetics Group at VHIO, and our Breast Cancer Group (PI, Cristina Saura).

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

Reflective of VHIO’s expertise in the PARPi field, VHIO faculty, including Violeta Serra, Judith Balmaña, Marta Castroviejo, Ana Oaknin (PI of VHIO’s Gynecological Malignancies Group, co-authored an elegant review (11) on a decade’s development of these therapies, where we now stand, and where to next. This publication was first authored by Joaquin Mateo, PI of our Prostate Cancer Translational Research Group, who leads research aimed at potentiating PARPi in the treatment of prostate cancer.

Targeted multiplex proteomics towards more precisely matching patients to novel anti-cancer medicines

Paolo Nuciforo, Principal Investigator, Molecular Oncology Group.

Research led by Paolo Nuciforo, Principal Investigator of our Molecular Oncology Group, also co-authored by VHIO PIs Ana Vivancos (Cancer Genomics), Rodrigo Dienstmann (Oncology Data Science Group – ODysSey), explored the promise of using targeted multiplex proteomics (TMP) as a novel approach to simultaneously measure a panel of proteins implicated in oncogenic processes, tumor suppression, drug metabolism and resistance. Also including tumor differentiation markers, this tool could guide standard diagnostic decision-making as well as render the selection of new targeted therapies and immune-based therapeutics for patients with metastatic colorectal cancer (mCRC) more precise.

In the article (12), the authors concisely review the strengths and limitations of the current ‘gold standard’ in accurately measuring multi-proteins in experimental samples, immunoassay, and outlines the downside of applying targeted proteomics using selected reaction monitoring mass spectrometry (SRM-MS). The researchers, also counting on the expertise of other VHIO investigators as well as the Vall d'Hebron University Hospital (HUVH) Pathology Department (directed by Santiago Ramón y Cajal), describe their findings by sub-chaptering each stage of their analyses.

Representing the very first study to measure the impact of quantitative targeted proteomics in precision oncology against mCRC, they analyzed protein biomarker profiles and integrated the results obtained with the available clinical, pathological and genomic data towards advancing precious insights into predictive and prognostic markers. Not only do they signpost that proteomics-steered drug development will expand treatment options for patients who are eligible to participate in early phase clinical trials, particularly considering the increasing emergence of promising antibody-drug conjugates (ADCs) and immune-based treatments, but also ring in the repurposing of proteomics as powerful anti-cancer armory in precision oncology.

Developing kinder & less disruptive treatments

As I reflect on our contributions made at the clinical level, here I select potentially practice-changing studies, including advances in novel clinical trial design that VHIO clinical investigators led or co-authored in 2019.

First, a trio of papers published in The New England Journal of Medicine that reported important advances against colorectal, ovarian, and pancreatic cancers, respectively.

Novel treatment combination for patients with BRAF-mutant metastatic colorectal cancer

Josep Tabernero, Director of Clinical Research at VHIO.

Led by our Gastrointestinal & Endocrine Tumors Group, findings presented on the ground at the 2019 Congress of the European Society of Medical Oncology (ESMO) here in Barcelona, showed that the triplet combination of the BRAF inhibitor, encorafenib, MEK inhibitor, binimetinib, and EGFR inhibitor, cetuximab, not only significantly improves overall survival but also increases objective response rates compared with standard of care in patients with BRAF V600E-Mutated Colorectal Cancer.

Published in parallel (13), the BEACON CRC phase III multicenter study, also counting on the expertise of co-author Elena Élez, Medical Oncologist and Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group, included patients with BRAF V600E-mutant metastatic colorectal cancer who had disease progression after one or two previous regiments. Seeking to potentiate BRAF-directed therapy in this patient population, study participants were randomly assigned to receive triplet therapy with encorafenib, binimetinib and cetuximab, or the investigator’s choice of either cetuximab and irinotecan or cetuximab and FOLFIRI.

Results showed significant clinical benefits with median overall survival of 9.0 months in the triplet group, 8.4 months in the doublet, and 5.4 months in the control arm. Regarding response rates, the researchers confirmed 26% in the triplet and 2% in the control. Importantly, tolerability of this novel combination was favorable.

These findings point to a potential paradigm shift in the treatment of this disease and warrant further investigation to better define the benefits of both the triplet and doublet combinations.

The promise of prolonged progression-free survival in newly diagnosed patients with high-grade ovarian cancer

Ana Oaknin, Principal Investigator, Gynecological Malignancies Group.

Also reported during the ESMO Congress 2019 and simultaneously published in NEJM, findings from the multinational phase III VELIA/GOG-3005 trial (14) led by Robert L. Coleman, University of Texas MD Anderson Cancer Center (USA), showed that the use of the poly (ADP-ribose) polymerase inhibitor veliparib plus first-line chemotherapy and as maintenance therapy improved progression-free survival (PFS) in patients with stage III or IV high-grade serous ovarian carcinoma versus induction chemotherapy alone.

The researchers, including Ana Oaknin, Principal Investigator of our Gynecological Malignancies Group, sought to establish whether PFS could be increased by adding veliparib as maintenance therapy in patients with newly high grade HGSC with and without germline BRCA mutations, and homologous recombination deficiency (HRD).

The trial included 1,140 patients from 210 sites in 10 countries who were randomly assigned to receive first-line induction chemotherapy with carboplatin/paclitaxel plus placebo followed by placebo maintenance of chemotherapy plus veliparib followed by veliparib maintenance.

Compared with the control group, the veliparib-throughout group had significantly prolonged PSF in the BRCA mutation and homologous recombination-deficiency cohorts, as well as the intention-to-treat population. This novel treatment approach shows that adding veliparib to standard chemotherapy and followed as maintenance therapy is able to statistically and clinically prolong PSF for patients recently diagnosed with high-grade ovarian cancer.

PARPi maintenance therapy against BRCA+ Metastatic Pancreatic Cancer

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

Headlining during the 2019 Annual Meeting of the American Society of Clinical Oncology (ASCO), 31 May-04 June (Chicago, USA), results from the POLO phase III study (15) co-authored by Teresa Macarulla, Medical Oncologist and Principal Investigator of our Gastrointestinal & Endocrine Tumors Group, also published in parallel in NEJM, and were selected to feature in ASCO’s Media Program.

This international trial, led by Hedy L. Kinder (University of Chicago), was designed to evaluate the efficacy of maintenance therapy with a PARP inhibitor olaparib in patients with germline BRCA-mutated metastatic pancreatic cancer. Showing that this approach significantly improved progression-free survival (PFS) compared with placebo among these patients, these findings could represent new hope and open up new treatment avenues for this patient population.

Specifically, approximately 6-8% of patients with pancreatic cancer are carriers of this mutation and could stand to benefit from this therapeutic approach. Expanding the group of patients who might also gain from Olaparib, beyond those who have a germline BRCA1 or BRCA2 mutation, could also be of interest.

Prolonging PFS in previously untreated PD-L1-positive metastatic renal cell carcinoma patients

Cristina Suarez, Medical Oncologist and Clinical Investigator, Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group.

Results of the phase III IMmotion151 trial presented by Brian Rini, Taussig Cancer Institute, Cleveland Clinic (USA) at ASCO 2019, which published simultaneously (16), show promise in improving progression-free survival (PFS) by combining monoclonal antibodies atezolizumab and bevacizumab versus sunitinib alone in patients with previously untreated, programmed cell death ligand (PD-L1)-positive, metastatic renal cell carcinoma.

The trial enrolled 915 patients from 152 sites in 21 countries who were randomly assigned to receive atezolizumab plus bevacizumab or sunitinib. The investigators, including Cristina Suarez, Medical Oncologist and Clinical Investigator of our Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site directed by Joan Carles, reported that not only did the combinatorial therapy prolong PSF in this patient population, if also showed a favorable safety profile, pointing to this approach as a first-line treatment option for selected patients with advanced renal cell carcinoma.

Clinical trial design in the era of precision oncology

In 2019, results of WINTHER clinical trial, Genomic and transcriptomic profiling expands precision medicine -the first study pioneered by the WIN Consortium published in Nature Medicine (17). Led by VHIO, findings showed that RNA profiling together with DNA testing matches more patients with advanced cancer to personalized anti-cancer therapies than DNA profiling for tumor mutations alone.

Carried out in collaboration with other leading members of WIN, co-authors including Jordi Rodón, Clinical Investigator at the MD Anderson Cancer Center and Associate Investigator of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, and Irene Braña, Phase I Investigator of the same Unit, showed that patients treated with a drug or regimen more closely matched to the molecular profile of their respective tumors, do better. By assessing RNA as an important adjunct to DNA profiling for determining precision treatments, WINTHER rings in a new era for personalized medicine in oncology.

Endorsed by the Cancer Core Europe Consortium (CCE), and officially launched during its 4th Annual Meeting, hosted by VHIO in 2019, the Basket of Baskets (BoB) two-stage clinical trial study promises a more flexible and adaptive model in order to significantly accelerate patients’ access to an array of novel therapeutics. As the first European multi-modular academic trial, BoB integrates molecular prescreening, the development of novel diagnostic tests including ctDNA, with the assessment of targeted therapies matched to those patients who will be most likely to benefit from them.

Elena Garralda, Director of VHIO's Molecular Therapy of Cancer (UITM) - "la Caixa".

BoB is divided into two separate parts: advanced molecular diagnosis or screening, i-Profiler, and the therapeutic phase, i-Basket. In the former patient tumor samples are analyzed for genetic profiling to identify the specific alterations of each individual tumor, followed by bioinformatics analyses to gauge the clinical relevance of a particular treatment tailored to these alterations, with the option of adding extra modules with other anti-cancer medicines currently under development.

Patients identified with the alteration/s included in BoB’s i-Basket phase, and who meet the inclusion criteria, enter this second part. Each module focuses on a different treatment (either as monotherapy or in combination), and will have a different sponsor/coordinator. The first module is evaluating atezolizumab in a molecularly-selected population recruited this year, and funding to assess FGFR inhibition in specific patients has been secured.

Ana Vivancos, Principal Investigator, Cancer Genomics Group.
Rodrigo Dienstmann, Principal Investigator, Oncology Data Science Group (ODysSey).

At VHIO, this novel trial is being carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Elena Garralda, and counts on the expertise of several VHIO investigators including Jordi Rodón and Irene Braña, Associate Investigator and Phase I Investigator of the same Unit, respectively, as well as Rodrigo Dienstmann, PI of VHIO’s Oncology Data Science Group (ODysSey), and Ana Vivancos who leads our Cancer Genomics Group.

Ana’s group is also appointed as co-lead of CCE’s Genomics Taskforce, responsible for the alignment of genomic testing across all member institutions.

In addition to my pick of practice changing data and projects here, please also see an additional selection detailed in my introductory pages as Director of VHIO’s Clinical Research Program, as well as the Paper pick section of each particular group; selected by our respective Principal Investigators.


The power of cross-border collaboration

In addition to our participation in the WIN Consortium and Cancer Core Europe, we also belong to several other important collaborations. 2019 celebrated the launch of an additional five pioneering projects:

The OPTIMISTICC Grand Challenge -Opportunity To Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer- is a five-year consortium funded by Cancer Research UK’s Grand Challenge, led by Matthew Meyerson, the Dana-Farber Cancer Institute-Harvard Medical School, and Wendy Garrett, Harvard T.H. Chan School of Public Health (USA).

Aimed at better understanding the difference between a healthy microbiome and a microbiome associated with the development of colorectal cancer, the co-investigators from the US, Canada, the UK, Netherlands, and Spain, are seeking to identify ways to manipulate this collection of microorganisms to better prevent and treat cancer. The project partners, including VHIO, are exploring this through clinical trials of new interventions based on the research results.

EUCanCAN – the European-Canadian Cancer Network, led by the Barcelona Supercomputing Center - BSC (Spain), comprises a total of eighteen partners, including VHIO, to pursue the homogeneous analysis, management and exchange of genomic-driven oncology data to advance precision medicine in cancer.

Jointly funded by the European Union’s Horizon 2020 research and innovation programme and the Canadian Institutes of Health, this four-year project is coordinated by David Torrents at the BSC, and strives to provide a functional platform for federated genome analysis systems towards efficiently analyzing, managing, sharing and reusing mass genomic data at the global level.

Immune-Image is a twenty two stakeholder-strong consortium incorporating public and private partners, including VHIO and the Vall d’Hebron Institute of Research (VHIR). Powered by the Innovative Medicines Initiative Joint Undertaking (IMI 2 JU), this initiative is led by Roche and coordinated by Albert Windhorst, Amsterdam University Medical Center (VUmC), The Netherlands.

Set to run for an initial duration of five years, this project is entitled Specific imaging of immune cell dynamics using novel tracer strategies, and seeks to develop a novel non-invasive imaging strategy for assessing immune cell activation and dynamics in oncology and inflammatory disease.

Funded by the European Union’s Horizon 2020 research and innovation programme, the CELAC and European Consortium for a Personalized Medicine Approach to Gastric Cancer (LEGACy) is a four-year project spearhead by Andrés Cervantes, the INCLIVA Health Research Institute (Spain), in partnership with ten other members including VHIO.

Focused on advancing personalized medicine against gastric cancer, this project aims to improve diagnosis and treatment by using data obtained through extensive research in four EU countries and four countries within the Community of Latin American and Caribbean States (CELAC) States, by applying personalized medicine at the three levels of prevention.

RADprecise

RADprecise - Personalized radiotherapy: Incorporating cellular response to irradiation in personalized treatment planning to minimise radiation toxicity, is supported by funding received through ERAPerMed’s co-funded Joint Translational Call 2018 and was founded by seven leading organisations, including VHIO. This three-year project aims to render radiotherapy more precise by incorporating data from finely-tuned predictive models to pre-identify toxicity based on insights from multiple biomarkers of radiosensitivity in individual patients.

Led by Principal Investigator, Jenny Chang-Claude from the German Cancer Research Center (DKFZ), project partners are applying findings at the clinical level by integrating a treatment planning system.

The Last Word

As VHIO's Director, I am honored and privileged to lead and work with our many research talents and dedicated healthcare professionals in oncology. Without our multidisciplinary and translational teams, cross-border collaborations and partnerships, and the passion and drive that unite us all in our ambition to solve cancer sooner, our Institute would cease to exist.

That same sustained devotion and belief is also shared in equal measure by our wonderful institutional supporters – 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 intense desire as we do: to reduce the devastating burden that this disease has on society.

The promotional poster for Pau Donés' final fundraising concert, December 2019.

Regarding the amazing support that we receive from individuals, I am very sad to report 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, succumb to his disease in 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.

On behalf of VHIO, I take this opportunity to gratefully thank him for his support of research in oncology, his enormous generosity, commitment and boundless positivity, creativity, zest and zeal.

To raise funds for research at VHIO, he not only organized four sell-out concerts, but also valiantly spoke out to raise awareness on and around cancer. He really was a true inspiration to us all.

As this report goes to press, the latest statistics issued by the European Commission’s Joint Research Centre (18) estimate that the cancer burden in EU-27 countries has risen to 2.7 million cases (all types, excluding non-melanoma cancer) and 1.3 million deaths in 2020.

Regarding the tick-tock to 2025 and the current COVID-19 pandemic, I believe that we will overcome this global virus and progress to even bigger success in our efforts to combat cancer through 2025 and beyond. We can, and will, do even better.

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


References
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  5. Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, Rubio-Perez C, Iurlaro R, Arias A, Cuartas I, Sala-Hojman A, Escudero E, Martínez-Ricarte F, Huber-Ruano I, Nuciforo P, Pedrosa L, Marques C, Braña I, Garralda E, Vieito M, Squatrito M, Pineda E, Graus F, Espejo C, Sahuquillo J, Tabernero J, Seoane J. LIF regulates CXCL9 in tumor-associatedmacrophages and prevents CD8 + T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun. 2019 Jun11;10(1):2416.
  6. Beaulieu ME, Jauset T, Massó-Vallés D, Martínez-Martín S, Rahl P, Maltais L, Zacarias-Fluck MF, Casacuberta-Serra S, Serrano Del Pozo E, Fiore C, Foradada L, Cano VC, Sánchez-Hervás M, Guenther M, Romero Sanz E, Oteo M, Tremblay C, Martín G, Letourneau D, Montagne M, Morcillo Alonso MÁ, Whitfield JR, Lavigne P, Soucek L. Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy. Sci Transl Med. 2019 Mar 20;11(484):eaar5012.
  7. Lambies G, Miceli M, Martínez-Guillamon C, Olivera-Salguero R, Peña R, Frías CP, Calderón I, Atanassov BS, Dent SYR, ArribasJ, García de Herreros A, Díaz VM. TGFß-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. Cancer Res. 2019. Jan 1;79(1):33-46.
  8. Kang SA, Guan JS, Tan HJ, Chu T, Thike AA, Bernadó Morales C, Arribas J, Wong CY, Tan PH, Gudi M, Putti TC, Sohn J, Lim SH, Lee SC, Lim YP. Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab based neo-adjuvant therapy: A Retrospective and Multicentric Study. Clin Cancer Res. 2019 Apr 15;25(8):2588-2600.
  9. Capdevila J, Arqués O, Hernández Mora JR, Matito J, Caratù G, Mancuso FM, Landolf S, Barriuso J, Jimenez-Fonseca P, Lopez Lopez C, Garcia-Carbonero R, Hernando J, Matos I, Nuciforo P, Hernández-Losa J, Esteller M, Martínez-Cardús A, Tabernero J, Vivancos A, Palmer HG. Epigenetic EGFR Gene Repression Confers Sensitivity to Therapeutic BRAFV600E Blockade in Colon Neuroendocrine Carcinomas. Clin Cancer Res. 2020 Feb 15;26(4):902-909. Epub 2019 Oct 31.
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  11. Mateo J, Lord CJ, Serra V, Tutt A, Balmaña J, Castroviejo-Bermejo M, Cruz C, Oaknin A, Kaye SB, de Bono JS. A decade of clinical development of PARP inhibitors in perspective. Ann Oncol. 2019. Sep 1;30(9):1437-1447.
  12. Serna G, Ruiz-Pace F, Cecchi F, Fasani R, Jimenez J, Thyparambil S, Landolfi S, Elez E, Vivancos A, Hembrough T, Tabernero J, Dienstmann R, Nuciforo P. Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer. Sci Rep. 2019 Sep 19;9(1):13568.
  13. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. 2019. N Engl J Med. 381(17): 1632 - 1643.
  14. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CºK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. 2019. N Engl J Med. 381(25): 2403 - 2415.
  15. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. 2019. N Engl J Med. 381(4): 317 - 327.
  16. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ, IMmotion151 Study Group. 2019. Lancet. 393(10189): 2404 – 2415.
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  18. ECIS – European Cancer Information System: https://ecis.jrc.ec.europa.eu/

VHIO’s Scientific Report 2019:
tick tock toward 2025

Championed by VHIO’s Director, Josep Tabernero, our Program Directors, Principal Investigators, and Heads of our Transversal Clinical Trials Core Services & Units, spearhead efforts aimed at solving cancer sooner. They lead their respective groups and teams to turn current obstacles in oncology into opportunities, and look ahead to the future to anticipate the challenges ahead.

With the year 2025 rapidly approaching – the deadline to attain the World Health Organization’s 9 voluntary global targets for noncommunicable diseases – they continue to drive and accelerate research advancements that will ultimately contribute to meeting target 1 in cancer, namely, a 25% relative reduction in overall mortality from this disease.

Introducing VHIO

Who we are and what we do

VHIO's Organigram 2019

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

Its optimal organizational structure allows VHIO talents to continue to both anticipate and tackle the many unresolved questions in ultimately outsmarting the multifaceted, heterogeneous and complex disease that is cancer:

VHIO in 2019: tick tock toward 2025

VHIO's translation toward precision oncology:
a little more on how we did it in 2019

VHIO’s Director, Josep Tabernero: welcoming all stakeholders in oncology to our CELLEX building – the home and heart of the Vall d'Hebron Institute of Oncology (VHIO).

Our public patron, the Generalitat de Catalunya (the Government of Catalonia) – together with the Vall d’Hebron University Hospital (HUVH) – represented by its Departments of Health (Departament de Salut), and Industry and Knowledge (Departament de Empresa I Coneixement), 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, 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, 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. For further details see: New funding and projects in 2019


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, now promotes the purely translational and multidisciplinary model for which VHIO is famed.

CELLEX also financed the construction and infrastructures of our state-of-the-art building – the CELLEX Center – that was completed 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 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 expand our groups in order to pursue new emerging research areas including immunology & immunotherapies, as well as fortify our research structure.

As importantly, thanks to CELLEX, our cutting-edge Animal Facility has spurred the more precise development of our predictive cancer models. Incorporating the latest platforms and technologies for analyzing small animals of human disease, this facility that we share with other colleagues across the Vall d'Hebron Barcelona Hospital Campus, has enabled us to further establish VHIO as a European reference in cancer modelling.

We take this opportunity to congratulate CELLEX as a most worthy recipient of one of the Government of Catalonia’s Josep Trueta medals in 2019. Awarded to healthcare professionals and organizations that have significantly contributed to the advancement of healthcare, this recognition honors CELLEX’s many initiatives that have accelerated biomedical research and improved healthcare across Catalonia.


Support received from the Fundación FERO (FERO Foundation), has, from the very beginning, enabled science of excellence at VHIO as well as promoted the careers of up-and-coming talents in oncology through its annual 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 Professor, Violeta Serra, PI of VHIO’s Experimental Therapeutics Group, Joaquín Arribas, Co-Director of our Preclinical and Translational Program and ICREA Professor, who also heads our Growth Factors Group, and Sandra Peiró, who leads our Chromatin Dynamics 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 develop our Droplet Digital PCR (ddpCR) Bio-Rad Technology platform and advancing research into the more effective and less invasive tracking of cancer by liquid biopsy.

Regarding its Annual Awards for Translational Research, a total of ten of our research scientists have been honored with this prize: 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), and Joaquin Mateo, Violeta Serra and Judith Balmaña (2019).

More specifically, VHIO’s 2019 awardees have been prized to continue to develop the liquid biopsy of cancer; pioneered by our Institute – also driven by the VHIO-FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV). For more information about these innovative undertakings spearhead by VHIO’s Joaquin Mateo, PI of our Prostate Cancer Translational Research Group, Violeta Serra, PI of our Experimental Therapeutics Group, and Judith Balmaña, PI of Hereditary Cancer Genetics.

The aforementioned DIAMAV Program powered by FERO, enables VHIO’s clinical investigators and cancer researchers to identify specific molecular risk factors better predict the potential efficacy of specific agents tailored to each particular tumor, further advance insights into the more effective and less invasive tracking of disease by liquid biopsy, and develop cancer diagnostics for the early detection of disease.

Lastly, but by no means least, FERO also promotes the importance of cancer research through the organization of several public engagement and annual fundraising initiatives and events. As an example in 2019, it organized a ‘swimathon’, Marnaton 4 FERO, to raise money for research led by Héctor G. Palmer (PI of VHIO’s Stem Cells & Cancer Group) into the early detection of cancer recurrence by liquid biopsy.


Thanks to the support received from the ”la Caixa” Foundation, VHIO’s Research Unit for Molecular Therapies of Cancer (UITM) – ”la Caixa” 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 co-direction of Josep Tabernero, VHIO’s Director -who also heads our Clinical Research Program- and Elena Garralda, PI 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 optimize treatment strategies using combinations of new agents with already existing ones.

Furthermore, in addition to various grants supporting several VHIO groups, 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 end of 2019 we announced a new 4-year VHIO-”la Caixa” Advanced Oncology Research Program (2020-2023). Marking the UITM turning ten in 2020 as well as the ringing in of a new VHIO decade, support received will further spur 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 rising focus fields in precision oncology.

Also thanks to the ”la Caixa” Foundation, our 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) – ”la Caixa”Clinical Research Onco-Hematology Unit will enable Maria Queralt Gorgas’ team to provide even higher quality pharmaceutical care and services, as well as continue to meet all regulatory requirements.

Finally, 2019 also celebrated the launch of our VHIO –”la Caixa” Scientific Seminars Series. This 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.


Also 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 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. Leading these research efforts are Alena Gros and Elena Garralda, PIs of our Tumor Immunology & Immunotherapy, and Early Clinical Drug Development Groups, respectively.

VHIO has co-founded various translational projects linked to the early clinical development phases of immunotherapy. These pioneering research endeavors are currently underway. Focus areas this year include the characterization of hyperprogressive disease with immunotherapy to advance insights into this phenomenon, as well as establishing a radiomic signature to predict response to immunotherapy; carried out in collaboration with Raquel Perez-Lopez, PI of our Radiomics Group

Shining a light on the BBVA Foundation’s dedication to spurring of progress against cancer, and indeed advances in cardiovascular disease, neurodegenerative diseases, as well as metabolic disorders, it received a prized bestowed by the national periodical ABC’s Health Section under the category of Foundation of the Year. Specifically, this Premio ABC Salud recognizes the Foundation’s support of biomedical research programs of excellence, including VHIO and our aforementioned BBVA CAIMI program.


Located within the Vall d’Hebron Barcelona Hospital Campus, our researchers closely collaborate and interact with Vall d’Hebron University Hospital (HUVH) physician-scientists. Translational science and clinical research are therefore tightly connected which promotes superb interaction and teamwork which, in turn, accelerates the bench-bedside-bed 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 pioneering model and programs, 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: at a glance

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

Driving and applying powerful technology platforms

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 drive faster 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 (Prescreening Program). Her lab is equipped with an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and three NextGen Sequencers; MiSeq, NextSeq and HiSeq2500, Illumina.

Our Prescreening Program, pioneered by Ana’s Group in collaboration with VHIO’s Molecular Oncology Group led by Paolo Nuciforo, Early Clinical Drug Development Group headed by Elena Garralda, and Oncology Data Science (ODysSey) Group directed by Rodrigo Dienstmann, together with Susana Aguilar and Jenifer Gonzalez, performs molecular profiling in up to 1500 patients each year as potential candidates for enrollment in our Phase I clinical trials led by VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, also championed by Elena Garralda.

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

Patients’ suitability for inclusion in any given clinical trial is assessed based on their respective genomic or pathologic profile. Ana’s group has developed and routinely implemented several tests for this program. Two are based on NGS: an Amplicon-seq approach to sequence 67 genes as well as a 450-gene capture panel (Illumina).

The group uses nCounter (Nanostring) for their RNA-based gene fusion panel, with the capacity of detecting over 100 recurrent gene fusions (also enabling the assessment of of gene expression patterns in tumors), and Copy Number Alterations panel evaluating a 59 panel for genes with frequent gains or losses in cancer. Reflective of excellence and quality, they have attained ISO 15189 flexible accreditation for the Amplicon-seq testing method, and will soon obtain this accreditation for their large 450-gene capture panel.

Importantly, our prescreening efforts have established VHIO as one of the few centers in Europe to run such a comprehensive program. We will continue to extend our efforts to an increasing number of patients thanks to expanded collaborations with other centers.

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, 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.



The hub and heart of VHIO's early clinical drug development: our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”

VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”. Middle image: Elena Garralda, UITM’s Director.

VHIO continues to establish itself as a leading reference in progressing drug development and targeted therapies against cancer. Since its inauguration in 2010, the UITM, under the direction of Elena Garralda as Executive Director, alongside Josep Tabernero, has rapidly become as one of the few comprehensive facilities in Europe to up the tempo in transforming latest discovery into improved outcomes for patients.

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 the UITM is driven by Elena’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 witah existing ones.

In 2019, this Unit participated in 162 ongoing phase I clinical trials, 23 of which were Basket trials. UITM’s facilities, coupled with its multidisciplinary clinical teams, enable VHIO to continuously expand its portfolio of early phase studies including complex trials such as ‘baskets’. As an example, this year Elena’s team initiated a novel academic study endorsed by the Cancer Core Europe (CCE) Consortium, and co-funded by pharmaceutical companies. The Basket of Basket (BoB) trial –designed and led by VHIO- integrates cutting-edge molecular prescreening the development of new diagnostic tests such as circulating DNA with the testing of targeted therapies in populations of patients with identified molecular alterations in their tumors and a high probability of benefiting from the selected treatments.

This year we opened 46 new trials; 6 as Baskets. 499 patients were recruited, 241 of whom were enrolled in immunotherapy clinical studies. Our Clinical Trials Office, directed by Gemma Sala and also located in the patient environment of the Vall d’Hebron University Hospital (HUVH), coordinates a large portfolio of Phase I, Baskets, Phase II & III clinical trials. In 2019 the number of patients included in these trials totaled at 1122 across 425 actively recruiting trials.

Research at our 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.

Concerning novel immunotherapeutics, our Unit’s Taskforce spearheads 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.



VHIO's direct access to cancer patients: crucial to 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.


Transformative cancer research of excellence

2019 celebrated a record-breaking year in terms of the impact of our cancer science. 333 scientific articles were published by VHIO researchers as corresponding/senior or co-authors with a cumulative Impact Factor (IF) totaling at 3806.

This figure reflects an increase in the importance of VHIO’s contribution to the oncology field.


Predictive powers, promising biomarkers & novel drug targets

As documented throughout our Preclinical & Translational Program pages within this Scientific Report, several VHIO studies and research lines continue to mark important progress in advancing cancer modelling, rendering predictive biomarkers more precise, and bringing new drug-targets closer to the clinic.

A few highlights in 2019:

Building on previous VHIO research pioneered by our Gene Expression & Cancer Group, results from another study* led by Joan Seoane, Co-Program Director of Preclinical and Translational Research at VHIO, and ICREA Research Professor, have shown that the blockade of the multi-functional cytokine LIF induces tumor-infiltrating T Cells to hone in on and eliminate cancer.

Novel agent MSC-1 reactivates an immune call by LIF blockade.

Developed by VHIO, novel agent MSC-1 inhibits LIF and has now been evidenced to have a dual mechanism of action. First, in tumors expressing high levels of LIF, this protein promotes the proliferation of cancer stem cells. LIF blockade eliminates these tumor-initiating stem cells, putting the brakes on metastatic cell spread and cancer recurrence. Additionally, elevated LIF expression disables the anti-tumor alarm system and stops the immune system from thwarting cancer’s plans. Blocking LIF reactivates the alarm to call an anti-tumoral immune response.

This research, carried out in collaboration with other VHIO groups and departments at the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, has now culminated in a Phase I clinical trial currently assessing the safety and efficacy of LIF inhibitors in patients across three sites: HUVH, Memorial Sloan Kettering Cancer Center (MSKCC – New York, USA), and the Princess Margaret Cancer Center (Toronto, Canada).

* Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, Rubio-Perez C, Iurlaro R, Arias A, Cuartas I, Sala-Hojman A, Escudero E, Martínez-Ricarte F, Huber-Ruano I, Nuciforo P, Pedrosa L, Marques C, Braña I, Garralda E, Vieito M, Squatrito M, Pineda E, Graus F, Espejo C, Sahuquillo J, Tabernero J, Seoane J. LIF regulates CXCL9 in tumor-associatedmacrophages and prevents CD8 + T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun. 2019 Jun11;10(1):2416.


In 2019, our Growth Factors Group, led by Joaquin Arribas, Co-Program Director of Preclinical & Translational Research at VHIO and ICREA Research Professor, has initiated a new line of research focused on generating novel chimeric antigen receptors (CARs), as a strategy to use the immune system of patients to eradicate tumors. This approach has been enabled by the insights they previously gained by developing and characterizing bispecific antibodies. Specifically, these CARs are directed against the p95HER2 protein which is only found in some breast and gastric tumors, though completely absent in normal tissues.

Also this year, the group’s expanding platform of breast and pancreatic cancer patient-derived experimental models has led them to identify novel mechanisms of resistance to anti-cancer therapies*, as well as seek out biomarkers of sensitivity to precision therapies **, in collaboration with national and international groups.

*Lambies G, Micelio M, Martínez-Guillamon C, Olivera-Salguero R, Peña R, Frías CP, Calderón I, Atanassov BS, Dent SYR, ArribasJ, García de Herreros A, Díaz VM. TGFß-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. Cancer Res. 2019.Jan 1;79(1):33-46.

** Kang SA, Guan JS, Tan HJ, Chu T, Thike AA, Bernadó Morales C, Arribas J, Wong CY, Tan PH, Gudi M, Putti TC, Sohn J, Lim SH, Lee SC, Lim YP. Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab based neo-adjuvant therapy: A Retrospective and Multicentric Study. Clin Cancer Res. 2019 Apr 15;25(8):2588-2600.


One translational VHIO study published in 2019* represents an important forward step in driving the Omomyc mini-protein closer to the clinic. Findings first authored by Marie-Eve Beaulieu, CSO and Co-Founder of VHIO-born spin-off Peptomyc, directed by Laura Soucek, PI of our Mouse Models of Cancer Therapies Group, ICREA Research Professor and Co-Founder and CEO of Peptomyc, evidence the Omomyc mini-protein as the first efficient and tolerable MYC inhibitor for the treatment of non-small cell lung cancer (NSCLC).

For the very first time the authors establish that the Omomyc mini-protein can be purified and administered in vivo, rapidly reaching the tumor site. Results show that it successfully inhibits its target, leads to reduced tumor grade and promotes regression of existing disease.

Thanks to Marie-Eve’s particular expertise in peptide design and production, the team succeeded in scaling up the purification process of the mini-protein and re-assessing its therapeutic activity via intravenous administration. Its systemic delivery unleashes the anti-cancer potential of Omomyc and extends its application to the treatment of other tumors and metastases.

The authors suggest that Omomyc may attack tumors not only through the blocking of proliferation and the induction of apoptosis, but also by triggering an immune response. The inhibitor can alter the profile of molecules released by cancer to trick the immune system, and may increase the infiltration of T lymphocytes into the tumor. This is relevant since immunotherapy is showing increasing promise in the treatment of several tumor types, but not all. The potential capacity of Omomyc to recruit immune cells at the tumor site, ‘spoilered’ in the study, indicates that it could also synergize and resensitize resistant tumors to immune-based therapies.

* Beaulieu ME, Jauset T, Massó-Vallés D, Martínez-Martín S, Rahl P, Maltais L, Zacarias-Fluck MF, Casacuberta-Serra S, Serrano Del Pozo E, Fiore C, Foradada L, Cano VC, Sánchez-Hervás M, Guenther M, Romero Sanz E, Oteo M, Tremblay C, Martín G, Letourneau D, Montagne M, Morcillo Alonso MÁ, Whitfield JR, Lavigne P, Soucek L. Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy. Sci Transl Med. 2019 Mar 20;11(484):eaar5012.


3D rendering of microPET/CT imaging of lungs of a tumor-bearing mouse 24 hours after intranasal administration of 2.37 mg/kg Omomyc-DFO-89Zr. CT data are displayed in gray scale and Omomyc-DFO-89Zr microPET data in color scale. The color scale is expressed as %ID/g for Omomyc-DFO-89Zr uptake.

VHIO’s Stem Cells & Cancer Group directed by Héctor G. Palmer, has made important progress in identifying molecular mechanisms conferring sensitivity or resistance to therapies in order to more precisely stratify patients for enrollment in clinical trials.

More specifically, working in close collaboration with other VHIO groups and pharmaceutical companies, they seek to identify the molecular culprits that are responsible for the sensitivity or resistance to therapies blocking Wnt/beta-catenin, Notch, PI3K/AKT, EGFR/LGR5 or BRAF/MEK/ERK oncogenic signals.

As an example, in collaboration with other Spanish investigators and VHIO teams including our Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla), Cancer Genomics (PI: Ana Vivancos), Molecular Oncology Group (PI: Paolo Nuciforo), Early Clinical Drug Development Group (PI: Elena Garralda), they have studied epigenetic EGFR gene repression and the conference of sensitivity to therapeutic BRAFV600E blockade in colon neuroendocrine carcinomas; results of which were published this year*.

Based on this research, they are now designing new prescreening tests for a genetic-guided enrolment of patients in clinical trials. Importantly, their findings are helping to define new rational drug combinations to treat cancer patients with progressive disease.

*Capdevila J, Arqués O, Hernández Mora JR, Matito J, Caratù G, Mancuso FM, Landolf S, Barriuso J, Jimenez-Fonseca P, Lopez Lopez C, Garcia-Carbonero R, Hernando J, Matos I, Nuciforo P, Hernández-Losa J, Esteller M, Martínez-Cardús A, Tabernero J, Vivancos A, Palmer HG. Epigenetic EGFR Gene Repression Confers Sensitivity to Therapeutic BRAFV600E Blockade in Colon Neuroendocrine Carcinomas. Clin Cancer Res. 2020 Feb 15;26(4):902-909. Epub 2019 Oct 31.


Our Experimental Therapeutics Group, led by Violeta Serra, continues to mark important progress in gauging response to PARP Inhibitors (PARPi). Crucially, they have initiated the clinical validation of their RAD51predict test which is an immune-based assay performed on FFPE tumor sections.

Reflective of its promise in better gauging efficacy of PARPi in individual patients and eventual implementation as a diagnostic test, these efforts have most recently been awarded by the ERA PerMed progamme – an ERA-Net Cofund. This international project counts on the expertise of 32 partners from 23 countries, and is co-supported by the European Commission (Coordinator: Instituto de Salud Carlos III – ISCIII). The test is also being developed thanks to additional funding received this year from the la Caixa Foundation’s CaixaImpulse Consolidate 2019 program.

Directed by Violeta Serra, and led by Alba Llop, Post-Doctoral Fellow of our Experimental Therapeutics Group, the project not only centers on using RAD1 protein as a biomarker to help personalize cancer therapy, more precisely and rapidly predicting those patients who would be most likely to benefit from PARPi, better guide stratification in clinical trials, as well as extend PARPi for the treatment of additional tumor types beyond breast and ovarian cancers.

This present research builds on the successes of several previous projects, including the previous PARPiPRED (which was also funded by CaixaImpulse), aimed at identifying clinical biomarkers of sensitivity to PARP inhibitors, and is spearhead by Violeta Serra’s Experimental Therapeutics Group, in collaboration with Judith Balmaña’s Hereditary Cancer Genetics Group at VHIO, and our Breast Cancer Group (PI, Cristina Saura).

Reflective of VHIO’s expertise in the PARPi field, VHIO faculty, including Violeta Serra, Judith Balmaña, Marta Castroviejo, Ana Oaknin (PI of VHIO’s Gynecological Malignancies Group, co-authored an elegant review* on a decade’s development of these therapies, where we now stand, and where to next. This publication was first authored by Joaquin Mateo, PI of our Prostate Cancer Translational Research Group, who leads research aimed at potentiating PARPi in the treatment of prostate cancer.

*Mateo J, Lord CJ, Serra V, Tutt A, Balmaña J, Castroviejo-Bermejo M, Cruz C, Oaknin A, Kaye SB, de Bono JS. A decade of clinical development of PARP inhibitors in perspective. Ann Oncol. 2019. Sep 1;30(9):1437-1447.


One of the main challenges in more effectively treating triple-negative breast cancer (TNBC) is the acquisition of resistance to conventional chemotherapeutics. Research led by Sandra Peiró, Principal Investigator of our Chromatin Dynamics in Cancer Group, promises novel weaponry to more effectively combat cancer drug resistance in this particular tumor type.

This multi-center, Spanish study*, also carried out in collaboration with VHIO’s Growth Factors Group (PI: Joaquin Arribas) shows that, when compared to other breast cancer subtypes, the DNA of TNBC cells is much more compacted which renders it resistant to therapy. Results also indicate that chromatin decompaction could help to potentiate current therapies.

More specifically, the investigators identified oxidation of histone H3 as a key element in the induction of DNA compaction as well as discovered an association between compaction and resistance to anticancer agents.

They also discovered that LOXL2 inhibition could prevent chromatin compaction from occurring. This is particularly relevant since this compaction seems to frequently occur in TNBC, which hinders therapies from accessing the nucleus of cancer cells. While this occurs in other types of breast cancer, they found that in those patients with the triple-negative subtype who show most resistance to conventional therapies, LOXL2 is present in high quantities, suggesting its role as a mechanism of resistance.

* Cebrià-Costa JP, Pascual-Reguant L, Gonzalez-Perez A, Serra-Bardenys G, Querol J, Cosín M, Verde G, Cigliano RA, Sanseverino W, Segura-Bayona S, Iturbide A, Andreu D, Nuciforo P, Bernado-Morales C, Rodilla V, Arribas J, Yelamos J, de Herreros AG, Stracker TH, Peiró S. LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells. Oncogene. 2020 Jan;39(1):79-121. Epub 2019 Aug 28 2019.


Teaching an old protein new tricks, VHIO’s Tumor Biomarkers Group, directed by Josep Villanueva, has continued to pursue the potential of the HMGA1 protein as novel biomarker and drug target in breast cancer. Notably, his team has focused on developing monoclonal antibodies against this protein that could be used in the near future in cancer diagnostics and therapeutics.

Their expertise in this field led to a review article this year* exploring the future clinical implications of the unexpected secretion of HMGA1 in triple-negative breast cancer (TNBC).

* Méndez O, Pérez J, Soberino J, Racca F, Cortés J,Villanueva J. Clinical Implications of Extracellular HMGA1 in Breast Cancer. Int J Mol Sci. 2019. 20(23), 5950.


VHIO's Core Technologies Program, incorporates our Cancer Genomics, Molecular Oncology, and Proteomics Groups led by Ana Vivancos, Paolo Nuciforo, and Francesc Canals respectively. They are responsible for the development of VHIO's cutting-edge core technologies and platforms. These groups also pursue, implement, and develop their own independent research lines and projects.

As an example in 2019, research led by Paolo Nuciforo, Principal Investigator of our Molecular Oncology Group, co-authored by our Director, Josep Tabernero, and VHIO PIs Ana Vivancos (Cancer Genomics Group) and Rodrigo Dienstmann (Oncology Data Science Group – ODysSey), explored the promise of using targeted multiplex proteomics (TMP) as a novel approach to simultaneously measure a panel of proteins implicated in oncogenic processes, tumor suppression, drug metabolism and resistance. Also including tumor differentiation markers, this tool could guide standard diagnostic decision-making as well as render the selection of new targeted therapies and immune-based therapeutics for patients with metastatic colorectal cancer (mCRC) more precise.

In the article*, the authors concisely review the strengths and limitations of the current ‘gold standard’ in accurately measuring multi-proteins in experimental samples, immunoassay, and outlines the downside of applying targeted proteomics using selected reaction monitoring mass spectrometry (SRM-MS). The researchers, also counting on the expertise of other VHIO investigators as well as the Vall d'Hebron University Hospital (HUVH) Pathology Department (directed by Santiago Ramón y Cajal), describe their findings by sub-chaptering each stage of their analyses.

Representing the very first study to measure the impact of quantitative targeted proteomics in precision oncology against mCRC, they analyzed protein biomarker profiles and integrated the results obtained with the available clinical, pathological and genomic data towards advancing precious insights into predictive and prognostic makers.

Not only does this signpost that proteomics-steered drug development will expand treatment options for patients who are eligible to participate in early phase clinical trials, particularly considering the increasing emergence of promising antibody-drug conjugates (ADCs) and immune-based treatments, but also rings in the repurposing of proteomics as powerful anti-cancer armory in precision oncology.

*Serna G, Ruiz-Pace F, Cecchi F, Fasani R, Jimenez J, Thyparambil S, Landolfi S, Elez E, Vivancos A, Hembrough T, Tabernero J, Dienstmann R, Nuciforo P. Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer. Sci Rep. 2019 Sep 19;9(1):13568.


VHIO’s practice-changing data in 2019: at a glance

In addition to the myriad clinical highlights documented throughout this report, along with our various programs and units highlighted in the pages that follow this chapter, just some of the practice- changing data has been hand-picked by our Director, Josep Tabernero. First, five studies highlighted in his Foreword to this report (see sub-section Developing kinder & less disruptive treatments), and second, his additional selection featuring in his From the Program Director.

Concerning the former, here is a sample of our Clinical Research Program (80-109) studies that made the headlines in 2019:


Novel treatment combination for patients with BRAF-mutant metastatic colorectal cancer, led by our Gastrointestinal & Endocrine Tumors Group, headed by Teresa Macarulla and directed by Josep Tabernero: Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. 2019. N Engl J Med. 381(17): 1632 – 1643.


The promise of prolonged progression-free survival in newly diagnosed patients with high-grade ovarian cancer, co-authored by Ana Oaknin, Principal Investigator of our Gynecological Malignancies Group: Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CºK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. 2019. N Engl J Med. 381(25): 2403 - 2415.


PARPi maintenance therapy against BRCA+ Metastatic Pancreatic Cancer, co-authored by Teresa Macarulla, Principal Investigator of our Gastrointestinal & Endocrine Tumors Group: Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. Golan T; Hammel P; Reni M; Van Cutsem E; Macarulla T; Hall MJ; Park JO; Hochhauser D; Arnold D; Oh DY; Reinacher-Schick A; Tortora G; Algül H; O'Reilly EM; McGuinness D; Cui KY; Schlienger K; Locker GY; Kindler HL. 2019. N Engl J Med. 381(4): 317 - 327.


Prolonging PFS in previously untreated PD-L1-positive metastatic renal cell carcinoma patients, co-authored by Cristina Suarez, Medical Oncologist and Clinical Investigator of our Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site directed by Joan Carles: Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ, IMmotion151 Study Group. 2019. Lancet. 393(10189): 2404 – 2415.


Clinical trial design in the era of precision oncology, led by VHIO and co-authored by Tabernero, VHIO’s Director, Jordi Rodón, Associate Investigator of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, and Irene Braña, Phase I Investigator at the same Unit: Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Rodon J, Soria JC, Berger R, Miller WH, Rubin E, Kugel A, Tsimberidou A, Saintigny P, Ackerstein A, Braña I, Loriot Y, Afshar M, Miller V, Wunder F, Bresson C, Martini JF, Raynaud J, Mendelsohn J, Batist G, Onn A, Tabernero J, Schilsky RL, Lazar V, Lee JJ, Kurzrock R. 2019. Nat Med. 25(5): 751 - 751.


And there’s a lot more

For more 2019 highlights selected by our Preclinical & Translational Research Co-Program Directors and Director of Clinical Research Program, led by Joaquin Arribas, Joan Seoane, and Josep Tabernero, respectively, click here, as well as this year’s Foreword compiled by Josep Tabernero.

Please also refer to our Core Technologies Program as well as our individual VHIO group pages. Compiled by each respective Principal Investigator, they provide a summary of strategic goals, current research lines, as well as their most important developments/contributions and pick of papers for 2019.


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

FERO Foundation: driving advanced molecular diagnostics against cancer

Co-led by VHIO’s Director, Josep Tabernero in collaboration with Ana Vivancos, Paolo Nuciforo, and Rodrigo Dienstmann, Principal Investigators of our Cancer Genomics, Molecular Oncology, and Oncology Data Science (ODysSey) Groups, respectively, our VHIO-FERO Advanced Molecular Diagnostics Program (DIAMAV), is powered by the essential support received from one of our patrons, the FERO Foundation. This program seeks to advance molecular profiling in patients in order 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.

It is thanks to the backing received from FERO that VHIO has both established itself as a reference in prescreening and oncogenomics in Europe, and continues to extend its enabling technologies and platforms to an increasing number of individuals. More specifically, driven by VHIO’s Prescreening Program which also counts on the expertise of Elena Garralda, Principal Investigator of Early Clinical Drug Development, along with Susana Aguilar and Jenifer Gonzalez, molecular profiling is performed in up to 1500 patients each year.

Our researchers and clinical investigators identify specific molecular risk factors and better predict the potential efficacy of specific agents tailored to each particular tumor. Additionally, this knowledge better guides our multidisciplinary teams to assess and establish patients’ suitability for inclusion in early phase clinical trials led by VHIO’s Research Unit for Molecular Therapy of Cancer (UTIM) – ”la Caixa”, also headed by Elena Garralda.

Our VHIO-FERO DIAMAV Program enables us to lead one of the few centers in Europe to run such a comprehensive program, ensure that more of our patients can ultimately benefit from our powerful technology programs and approaches, further advance research into the more effective and less invasive tracking of cancer by liquid biopsy, as well as develop cancer diagnostics for the early detection of disease.

”la Caixa” Foundation: advancing research toward rendering anti-cancer medicines more precise

Building on the successes of the two previous VHIO-”la Caixa” Institutional 3-year Programs, at the end of 2019 we announced a new 4-year VHIO-”la Caixa” Advanced Oncology Research Program (2020-2023). Marking the UITM turning ten in 2020 as well as the ringing in of a new VHIO decade, support received will further spur 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 rising focus fields in precision oncology.

More specifically, our transformative research lines will continue to center of those areas showing particular promise in solving multiple questions that stand in the way of more effectively combating cancer. Just some of these scientific directions will include our continued unpicking of the complex role that the microbiome plays in cancer development, driving ‘big data’-derived insights, and devise and integrate cutting-edge platforms incorporating bioinformatics, biostatistics and machine learning applications in cancer prognosis and prediction, as well as harness the potential of Artificial Intelligence (AI) in the development of individually matched therapies.

In parallel with our plans to expand VHIO’s portfolio of clinical trials performed at our Research Unit for Molecular Therapy of Cancer – ”la Caixa”, directed by Elena Garralda, that have led and/or contributed to the approval of some 30 anti-cancer agents by the U.S. Food and Drug Administration (FDA), this Program will enable us to further advance and apply novel anti-cancer approaches and armory including liquid biopsy, RNA expression analysis, immune-based therapies, bispecific antibodies, oncolytic virus, and intratumoral therapy.

These efforts are driven thanks to the expertise of several VHIO groups and teams including our Early Clinical Drug Development, Cancer Genomics, Molecular Oncology, Oncology Data Science (ODysSey) Groups, led by Elena Garralda, Ana Vivancos, Paolo Nuciforo, and Rodrigo Dienstmann, respectively.

The matched dedication of our clinical and translational investigators across all VHIO groups, as well as VHIO’s Clinical Trial Office, headed by Gemma Sala, Clinical Trials Support Office, managed by Susana Muñoz, Clinical Research Oncology Nurses, spearhead by Nines Pañuelas, and Clinical Research Oncology Pharmacy Unit, led by Maria Queralt Gorgas, has also made the past decade’s total of 1060 Phase I and 1076 Phase II insightful studies possible.

Engineered to support education, trigger essential debate and promote data exchange across borders, the program is also dedicated to organizing expert seminars and international scientific meetings to come. As an example, our VHIO –”la Caixa” Scientific Seminars Series, launched in 2019. This 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.

BBVA Foundation: driving powerful programs to spur VHIO’s avant-garde translational research in precision oncology

Considering the tremendous successes of the very first VHIO-BBVA Foundation Program on Tumor Biomarkers Research that launched back in 2011, VHIO and the BBVA Foundation renewed their agreement in in 2017. Building on the achievements of the first program, our 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.

Under the leadership of our Director, Josep Tabernero, this ambitious project counts on the expertise of VHIO’s Elena Garralda (PI of VHIO’s Early Clinical Drug Development and Director of our Research Unit for Molecular Therapy of Cancer (UITM)), who heads up CAIMI’s clinical research, Alena Gros (PI, VHIO’s Tumor Immunology and Immunotherapy), who takes the lead on translational research, and Ana Vivancos (PI of our Cancer Genomics) who directs our internationally recognized Prescreening Program in collaboration with Paolo Nuciforo (PI of VHIO’s Molecular Oncology Group), and Rodrigo Dienstmann (PI of our Oncology Data Science – ODysSey Group), along with Susana Aguilar and Jenifer Gonzalez.

VHIO has co-founded various translational projects linked to the early clinical development phases of immunotherapy. These pioneering endeavors are currently underway. Just some focus areas include the development of cell-based therapies such as killer T cells for non-responders to current immunotherapies, characterizing hyperprogressive disease with immunotherapy to advance insights into this phenomenon, as well as establishing a radiomic signature to predict response to immunotherapy, in collaboration with Raquel Perez-Lopez, PI of our Radiomics Group.

At 'home' and away: advancing cancer science and medicine in collaboration

VHIO’s translational task-forcing.

Accelerating progress through team science

VHIO’s expert and interdisciplinary taskforces, coordinated by Alejandro Piris, our Scientific Manager, comprise comprehensive teams of oncologists, pathologists, other MD disciplines, preclinical and translational researchers, clinical research nurses, data curators and miners as well as study coordinators, and project managers, among others.

Cancer Core Europe (CCE) is a unique partnership aimed at addressing the cancer care research continuum. Launched in 2014, this working consortium represents a critical mass of activity for the successful integration of all cancer care information, clinical research and outcome research, led by the 6 founding partners and European comprehensive cancer centers of excellence: the Gustave Roussy Cancer Campus Grand Paris (Villejuif, France), Cambridge Cancer Centre (Cambridge, UK), Karolinska Institute (Stockholm, Sweden), Netherlands Cancer Institute – NKI (Amsterdam, The Netherlands), National Center for Tumor Diseases – DKFZ-NCT (Heidelberg, Germany), The National Cancer Institute of Milan (Italy), and VHIO.

CEE 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.

Endorsed by CCE and officially launched during its 4th Annual Meeting, hosted by VHIO, the Basket of Baskets (BoB) two-stage clinical trial study promises a more flexible and adaptive model in order to significantly accelerate patients’ access to an array of novel therapeutics. As the first European multi-modular academic trial, BoB integrates molecular prescreening, the development of novel diagnostic tests including ctDNA, with the assessment of targeted therapies matched to those patients who will be most likely to benefit from them.

BoB is divided into two separate parts: advanced molecular diagnosis or screening, i-Profiler, and the therapeutic phase, i-Basket. In the former patient tumor samples are analyzed for genetic profiling to identify the specific alterations of each individual tumor, followed by bioinformatics analyses to gauge the clinical relevance of a particular treatment tailored to these alterations, with the option of adding extra modules with other anti-cancer medicines currently under development.

Patients identified with the alteration/s included in BoB’s i-Basket phase, and who meet the inclusion criteria, enter this second part. Each module focuses on a different treatment (either as monotherapy or in combination), and will have a different sponsor/coordinator. The first module is evaluating atezolizumab in a molecularly-selected population recruited this year, 2019, and funding to assess FGFR inhibition in specific patients has been secured.

Updating on VHIO's participation in international consortia of excellence

Cancer Core Europe (CCE) is a unique partnership aimed at addressing the cancer care research continuum. Launched in 2014, this working consortium represents a critical mass of activity for the successful integration of all cancer care information, clinical research and outcome research, led by the 6 founding partners and European comprehensive cancer centers of excellence: the Gustave Roussy Cancer Campus Grand Paris (Villejuif, France), Cambridge Cancer Centre (Cambridge, UK), Karolinska Institute (Stockholm, Sweden), Netherlands Cancer Institute – NKI (Amsterdam, The Netherlands), National Center for Tumor Diseases – DKFZ-NCT (Heidelberg, Germany), The National Cancer Institute of Milan (Italy), and VHIO.

CEE 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.

Endorsed by CCE and officially launched during its 4th Annual Meeting, hosted by VHIO, the Basket of Baskets (BoB) two-stage clinical trial study promises a more flexible and adaptive model in order to significantly accelerate patients’ access to an array of novel therapeutics. As the first European multi-modular academic trial, BoB integrates molecular prescreening, the development of novel diagnostic tests including ctDNA, with the assessment of targeted therapies matched to those patients who will be most likely to benefit from them.

BoB is divided into two separate parts: advanced molecular diagnosis or screening, i-Profiler, and the therapeutic phase, i-Basket. In the former patient tumor samples are analyzed for genetic profiling to identify the specific alterations of each individual tumor, followed by bioinformatics analyses to gauge the clinical relevance of a particular treatment tailored to these alterations, with the option of adding extra modules with other anti-cancer medicines currently under development.

Patients identified with the alteration/s included in BoB’s i-Basket phase, and who meet the inclusion criteria, enter this second part. Each module focuses on a different treatment (either as monotherapy or in combination), and will have a different sponsor/coordinator. The first module is evaluating atezolizumab in a molecularly-selected population recruited this year, 2019, and funding to assess FGFR inhibition in specific patients has been secured.

Pioneering multi-modular trial design in oncology: the two-part Basket of Baskets (BoB) clinical study.

At VHIO, this novel trial is being carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Elena Garralda, and counts on the expertise of several VHIO investigators including Jordi Rodón and Irene Braña, Associate Investigator and Phase I Investigator of the same Unit, respectively, as well as Rodrigo Dienstmann, PI of VHIO’s Oncology Data Science Group (ODysSey), and Ana Vivancos who leads our Cancer Genomics Group. Ana’s group is also appointed as co-lead of CCE’s Genomics Taskforce and is responsible for the alignment of genomic testing across all member institutions.
www.cancercoreeurope.eu

WIN – Worldwide Innovative Networking in personalized cancer medicine, initiated by the Institut Gustave Roussy (France) and The University of Texas, MD Anderson Cancer Center (USA) is a non-profit, non-governmental organization incorporating 39 leading organizations representing all stakeholders in personalized cancer medicine covering 21 countries and 4 continents, united by their vision to deliver on the promise of effective, personalized cancer medicine to patients worldwide.

Under the tagline WINning together, WIN was formed on the premise that members can accomplish more together than each organization can achieve working alone. Aimed at improving cancer patients’ survival and quality of life, WIN members also collaboratively design and carry out global studies designed to achieve breakthroughs for cancer patients across the globe.

In 2019, results of WINTHER clinical trial, Genomic and transcriptomic profiling expands precision medicine -the first study pioneered by the WIN Consortium- published in Nature Medicine*. Led by VHIO, findings showed that RNA profiling together with DNA testing matches more patients with advanced cancer to personalized anti-cancer therapies than DNA profiling for tumor mutations alone.

Carried out in collaboration with other leading members of WIN, co-authors including Josep Tabernero, VHIO’s Director, Jordi Rodón, Clinical Investigator at the MD Anderson Cancer Center and Associate Investigator of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, and Irene Braña, Phase I Investigator of the same Unit, showed that patients treated with a drug or regimen more closely matched to the molecular profile of their respective tumors, do better. By assessing RNA as an important adjunct to DNA profiling for determining precision treatments, WINTHER rings in a new era for personalized medicine in oncology.

Rodon J, Soria JC, Berger R, Miller WH, Rubin E, Kugel A, Tsimberidou A, Saintigny P, Ackerstein A, Braña I, Loriot Y, Afshar M, Miller V, Wunder F, Bresson C, Martini JF, Raynaud J, Mendelsohn J, Batist G, Onn A, Tabernero J, Schilsky RL, Lazar V, Lee JJ, Kurzrock R. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat Med. 2019. 25(5): 751 - 751.
www.winconsortium.org

New in 2019

Announced at the beginning of 2019, the OPTIMISTICC Grand Challenge -Opportunity To Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer- is a 5-year consortium funded by Cancer Research UK’s Grand Challenge, led by Matthew Meyerson, the Dana-Farber Cancer Institute-Harvard Medical School, and Wendy Garrett, Harvard T.H. Chan School of Public Health (USA).

Aimed at better understanding the difference between a healthy microbiome and a microbiome associated with the development of colorectal cancer, the co-investigators from the US, Canada, the UK, Netherlands, and Spain, are seeking to identify ways to manipulate this collection of microorganisms to better prevent and treat cancer. They are exploring this through clinical trials of new interventions based on the research results.

It is thanks to the Grand Challenge Funding that the project partners, including VHIO, are able to pool the necessary expertise in order to establish how the microbiome influences a cancer’s response to treatment, develop new treatments that alter the microbiome, and decipher how an individual’s external environment may affect their microbiome.
www.optimisticc.org

EUCanCAN – the European-Canadian Cancer Network, led by the Barcelona Supercomputing Center - BSC (Spain), comprises a total of 18 partners from 5 different countries to pursue the homogeneous analysis, management and exchange of genomic-driven oncology data to advance precision medicine in cancer.

Jointly funded by the European Union’s Horizon 2020 research and innovation programme and the Canadian Institutes of Health, this 4-year project is coordinated by David Torrents at the BSC, and strives to provide a functional platform for federated genome analysis systems towards efficiently analyzing, managing, sharing and reusing mass genomic data at the global level.

The participating reference nodes, including VHIO, seek to process, store and share between 30-35 thousand patient samples across various tumor types. This consortium also promises to drive discovery into robust and clinically-relevant patterns of genomic variation in cancer, including predictive biomarkers.

Using existing and newly generated genomic and clinical insights within the consortium, the feasibility of EUCanCAN infrastructures and their interoperability are being tried and tested. This analysis is being carried out in partnership with some of the most active centers throughout Europe and Canada in genomic oncology across locally selected sites.

As an indicator of both the quality and promise of this project, the Global Alliance for Genomics and Health (GA4GH), selected it as one among seven world leading genomic data initiatives as its new Driver Projects for 2019
www.eucancan.com

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


Immune-Image is a 22 stakeholder-strong consortium incorporating public and private partners across 9 countries, including VHIO and the Vall d’Hebron Institute of Research (VHIR) from Spain. Powered by the Innovative Medicines Initiative Joint Undertaking (IMI 2 JU), this initiative is led by Roche and coordinated by Albert Windhorst, Amsterdam University Medical Center (VUmC), The Netherlands. Set to run for an initial duration of five years, this project is entitled Specific imaging of immune cell dynamics using novel tracer strategies, and seeks to develop a novel non-invasive imaging strategy for assessing immune cell activation and dynamics in oncology and inflammatory disease.

Main deliverables include developing clinically validated radio-and optical immunotracers for the monitoring and measurement of immune cell presence, activation status and trafficking, and designing and implementing a ready-to-use sustainable molecular imaging platform, incorporating standardized protocols, best practices, quantitative image analyses, immune-based tracking design and development.

By establishing a sustainable and flexible platform for molecular imaging of immune cells dynamics using a wide range of new tracer approaches, the team aims at potentiating immune-based therapies in precision oncology by enabling the ‘smart’ monitoring of these novel anti-cancer medicines.
www.immune-image.eu



Funded by the European Union’s Horizon 2020 research and innovation programme, the CELAC and European Consortium for a Personalized Medicine Approach to Gastric Cancer (LEGACy) is a 4-year project spearhead by Andrés Cervantes, the INCLIVA Health Research Institute (Spain), in partnership with 10 other members across 9 different countries including VHIO.

Focused on advancing personalized medicine against gastric cancer, this project aims to improve diagnosis and treatment by using data obtained through extensive research in four EU countries and four countries within the Community of Latin American and Caribbean States (CELAC) States, by applying personalized medicine at the three levels of prevention. This consortium seeks to implement a personalized medicine strategy at the first level of prevention, improve early gastric cancer detection at the second level of prevention, and improve treatment through the identification of high-risk populations.

Partners from Argentina, Belgium, Chile, Germany, Mexico, The Netherlands, Paraguay, Portugal and Spain are working together to design a cost-effective algorithm based on tumor biology data. Analysing more than 3 thousand cases in total, the project will also bring new insights into gastric cancer subtyping.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 825832.


RADprecise

RADprecise - Personalized radiotherapy: Incorporating cellular response to irradiation in personalized treatment planning to minimise radiation toxicity, is supported by funding received through ERAPerMed’s co-funded Joint Translational Call 2018* and was founded in 2019 by 7 leading organisations from Spain, Italy, Germany and France. This 3-year project aims to render radiotherapy more precise by incorporating data from finely-tuned predictive models to pre-identify toxicity based on insights from multiple biomarkers of radiosensitivity in individual patients.

Led by Principal Investigator, Jenny Chang-Claude from the German Cancer Research Center (DKFZ), project partners are applying findings at the clinical level by integrating a treatment planning system. Using parametric models and machine learning, clinical investigators from academia and health research, in collaboration with small and medium enterprises as well as patient advocates, are applying new biological data as well as readily available genomic information to develop models that can more precisely envisage adverse effects from radiotherapy to be validated in independent samples.

At preclinical level, RADPrecise’s predictive models will be key to tailoring therapy to each patient’s sensitivity. Given that an estimated 5-10 per cent of all patients receiving radiotherapy either as primary treatment or in combination will suffer severe adverse effects, with a further fifty per cent thought to experience less severe yet burdensome ones, this project prioritizes the identification of radiosensitive patients.
www.erapermed.eu

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 779282.


Strengthening our research, growing teams & fortifying facilities

As our Institute goes from strength to strength, and further develop its research lines and projects based on defined strategic directions, we continue to expand our scientific faculty as well as scientific support units and teams.

César Serrano, PI of VHIO’s Sarcoma Translational Research Group which launched in early 2019.

Illustrative of this growth, César Serrano who is a Medical Oncologist and Clinical Investigator of our Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group (directed by Joan Carles), took the reins as Principal Investigator of VHIO’s new Sarcoma Translational Research Group.

His group will seek to identify the critical molecular mediators of oncogenic signaling sarcomas, characterize response and resistance mechanisms to targeted therapies against these tumor types, as well as preclinically model and validate therapeutic strategies toward improving outcomes for patients in the clinic.

Alejandro Piris, Scientific Manager, VHIO’s Scientific Coordination Area.

Since it was established back in 2010, VHIO’s Scientific Coordination Area has evolved from an office providing basic support to a highly professional team with experience in both cancer research and project management. Directed by Alejandro Piris, his scientific coordination teams offer a range of personalized and professional support services to all VHIO groups, including identifying projects and helping to prepare proposals – all of which enable our researchers to file successful applications.

Also incorporating our Clinical Trials Support Office, led by Susana Muñoz, efforts center on identifying key opportunities, requirements and elements that should be taken into account, establish project deadlines, lead and coordinate proposal writing, and devise and implement contingency plans.

In 2019 Alejandro’s Area was awarded by the Catalonian Department of Health’s Strategic Plan for Research and Innovation in Health (PERIS). Newly introduced to PERIS’ Call this year, his team has received a Go Europe grant which promote international R&D&I. This funding awards research support units of accredited research institutes and centers belonging to the CERCA Institute (Institució CERCA Centres de Recerca de Catalunya), in order to extend their global reach, increase participation in international projects -EU’s Horizon 2020 Research and Innovation programme in particular- as well as improve their success rate and returns achieved through competitive grants.

Completed in 2019: the building of our Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa” – Clinical Research Onco-Hematology Unit. Pictured here, Maria Queralt Gorgas, Clinical Director of VHIO’s Clinical Research Oncology Pharmacy Unit.

It is thanks to the additional support received from the ”la Caixa” Foundation that the building of the new home of our Clinical Research Oncology Pharmacy Unit was completed in 2019. Providing the much needed additional space and equipped with the very latest technologies, the Molecular Therapy of Cancer (UITM) – ”la Caixa” – Clinical Research Onco-Hematology Unit will enable Maria Queralt Gorgas’ team to provide even higher quality pharmaceutical care and services, as well as continue to meet all regulatory requirements.


Awards & Recognitions 2019

International

The Web of Science Group announced its who’s who on the annual and global Highly Cited Researchers list for 2019, curated by the Institute for Scientific Information. Featuring among the 6216 top drawer leading researchers across the main 21 fields of the sciences and social sciences covered by the Essential Science Indicator (ESI), are VHIO’s Director, Josep Tabernero, and Enriqueta Felip, Principal Investigator of our Thoracic Tumors & Head and Neck Cancer Group.

For the fourth consecutive year Josep was selected for his exceptional advancements in cancer research under the category of Clinical Medicine that lists a total of 436 named leaders this year. Moving from her first listing under the Cross-Field category in 2018, Enriqueta joined Josep under the same field.

European

Just as our Director, Josep Tabernero, was completing his two-year term as President of the European Society of Medical Oncology (ESMO), 2018-2019, his renowned expertise and leadership as an international trailblazer in cancer science and medicine was called upon by EU’s Horizon 2020 program.

Succeeding the European Commission’s Horizon 2020 funding program for research and innovation, Horizon Europe is an ambitious €100 billion undertaking consisting of three main pillars – Excellent Science, Global Challenges and European Industrial Competitiveness, Innovative Europe, as well as the overarching ambition of Widening Participation and Strengthening the European Research Area.

Within Horizon Europe’s framework, five key research and innovation missions have been identified to increase the effectiveness of funding by pursuing clearly defined targets. They are: Adaptation to climate change including societal transformation, Cancer, Climate-neutral and smart cities, Healthy oceans, seas, coastal and inland waters, oil health and food.

Each mission has an appointed Board comprised of acclaimed leaders to shape and spur new research and innovation. All missions are also flanked by their respective Assemblies consisting of up to 30 high-level experts. The main role of these bodies is to help guide the Board members and provide an additional pool of ideas and knowledge to contribute to the successes of the respective missions. The Cancer panel consists of 26 members, including our Director, Josep Tabernero.

National

Josep Tabernero (left). Francesc Bosch (right).

In 2019 both VHIO’s Director, Josep Tabernero, and Francesc Bosch, Principal Investigator of our Experimental Hematology Group, featured among the Spanish edition of Forbes magazine’s pick of the 100 most influential leaders in healthcare across Spain.

Spanning 25 different specialties, Josep and Francesc were recognized under the categories of oncology and hematology, respectively. This accolade salutes their determined efforts aimed at advancing cancer research, precision medicine and care.

Announced at SEOM2019 -the annual Congress of the Spanish Society of Medical Oncology (SEOM), 22-25 October (Pamplona, Spain), Enriqueta Felip, Principal Investigator of VHIO’s Thoracic Tumors & Head and Neck Cancer Group, and her #SEOM2Punto0 team, were elected to join SEOM’s Board of Directors 2019-2021 under the presidency of Álvaro Rodríguez-Lescure, Head of the Medical Oncology Service of the Hospital General Universitario de Elche (Alicante, Spain).

VHIO’s Enriqueta Felip, Vice President of SEOM.

Led by Enriqueta, now Vice President of SEOM (to serve as President 2021-2013), her elected team will work alongside Álvaro and other Board Members to help expand the Society, its educational programs, innovation and relations with key stakeholders, and in collaboration with its expert working groups and supporters.

Presided by Sol Daurella who took up the reins as FERO Foundation’s President in 2019, FERO’s community gathered once again at the stunning Oval Room of Catalonia’s National Museum of Art (MNAC) for its annual fundraising gala dinner, sponsored by Andbank, and the 10th edition of FERO’s Annual Awards for Translational Research to promote cancer science of excellence and grow the careers of up-and-coming talents in oncology. This year, FERO honored three more VHIO investigators who now join VHIO’s previous seven Annual Award recipients.

Chaired by Andrés Cervantes, Director of Oncology at the Institute of Health Research INCLIVA (Valencia, Spain), the Foundation’s expert selection committee backed two pioneering VHIO projects aimed at developing the liquid biopsy of cancer. This year’s three prizes were presented to Joaquin Mateo, Violeta Serra and Judith Balmaña, Principal Investigators of VHIO’s Prostate Cancer Translational Research, Experimental Therapeutics, and Hereditary Cancer Genetics Groups, respectively, and Asís Palazón, Investigator at CIC bioGUNE (Bilbao, Spain).

Concerning VHIO’s duo of FERO Awards, one was jointly supported by the Ramón Areces Foundation, and the other by the hair care and styling company, ghd.

Andrés Cervantes (left) and Paloma Garcia Peña, Member of the Board of Trustees, the Ramón Areces Foundation (far right), present VHIO’s Joaquin Mateo with one of FERO’s Annual Awards for Translational Research 2019.

Since VHIO incorporated in-house BEAMing liquid biopsy RAS biomarker technology back in 2015, the first academic test center to do so, our Institute continue to make significant progress in validating and developing liquid biopsy and Droplet Digital PCR Bio-Rad technologies to better guide treatment decisions for our patients and less invasively ‘police’ disease over time, in real time.

VHIO’s contributions to-date have largely been possible thanks to the continued backing and belief received from FERO. These two most recent accolades will enable our scientists to further develop this approach towards ultimately delivering a more precise and rapid diagnosis of cancer, steering treatment decision making, and monitoring the course of cancer and response to therapy.

Specifically, Joaquin was awarded for his project that is set to test whether this novel approach can also help to predict the evolution of prostate cancer and in so doing, potentially detect disease relapse earlier as well as more ‘smartly’ monitor cancer’s next moves.

Left to right: José Baselga, FERO’s Honorary President, Thys Niermeyer, Director General, ghd Spain, presented VHIO’s Violeta Serra and Judith Balmaña with the first joint FERO-GHDproject Award.

To be spearhead by VHIO’s Violeta Serra and Judith Balmaña, the very first joint FERO-GHD project – a new initiative launched in 2019– will also develop liquid biopsy to monitor response to therapy and establish sensitivity of breast cancer patients with BRCA1/2 mutations to treatment with PARP inhibitors. The goal is to more effectively tailor personalized treatment regimens to the unique specificities of each particular cancer, more effectively tackle cancer drug resistance, as well as establish which patients would be most likely to benefit from these targeted therapies.

Projecting a live fundraising counter on the big screens during the event, FERO invited donations for a project aimed at more precisely monitoring the course of medulloblastoma – the most frequent of all pediatric brain tumors and a leading cause of cancer-related deaths in children.

Project lead Joan Seoane, Co-Program Director of Preclinical and Translational Research at VHIO and ICREA Professor, was invited to take center stage and provide a synopsis about this critical line of research. Building on his previous studies showing proof-of-concept that cerebrospinal fluid (CSF) can be exploited to characterize brain tumors as it contains ctDNA, Joan will seek to advance and apply this approach in order to better gauge the aggression of disease in these young patients, more faithfully guide treatment decisions, and use liquid biopsy-driven insights to develop and accelerate more precise and potent therapies against brain cancer.

Presented at a special award ceremony hosted by the Ramón Areces Foundation in Madrid, and presided by Ángeles Heras, Spanish Secretary of State for University Research, Development and Innovation, and President of the Foundation’s Board of Trustees, Florencio Lasaga, VHIO’s Joan Seoane, was also honored as recipient of one of its Annual National Awards, now in its XIX edition. These recognitions spur ‘home-grown’ science led by researchers of international excellence.

Joan Seoane, Co-Program Director of Preclinical and Translational Research at VHIO and ICREA Research Professor.

In the treatment of patients with metastatic non-microcytic lung cancers and melanoma, immune checkpoint inhibitors represent the ‘go to’ in systemic immunotherapy. Unfortunately, however, not all patients respond to these novel immune-based therapies, with the tumor microenvironment as a crucial and determining factor. Interestingly, intracranial lesions respond differently to these inhibitors than extracranial ones. This could suggest that the microenvironment modulates response to therapy in these patients.

Joan’s team, in collaboration with Enriqueta Felip, Principal Investigator of VHIO’s Thoracic Tumors & Head and Neck Cancer Group, and Eva Muñoz-Couselo, Medical Oncologist and Clinical Investigator of our Breast Cancer & Melanoma Group (PI: Cristina Saura), will analyze these patients’ brain metastases and compare them with their respective primary tumors in order to advance insights into the factors governing clinical response to immune checkpoint blockade in individual patients.

Maria Abad, Principal Investigator of our Cellular Plasticity & Cancer Group was awarded under the ”la Caixa” Health Research Call 2018 for a project entitled Defining the Role of Exosome-Secreted Micropeptides in Pancreatic Cancer.

Left to right: Hector Peinado (CNIO), Maria Abad (VHIO), Teresa Macarulla (VHIO), Bruno Costa Silva (Champalimaud Foundation).

Led by Maria, and jointly coordinated by Hector Peinado, Head of the Microenvironment and Metastasis Group, the Spanish National Cancer Research Centre (CNIO – Madrid), and Bruno Costa Silva, Head of Systems Oncology, Champalimaud Foundation (Lisbon, Portugal), the study will count on their renowned expertise in micropeptides, exosomes, and liver pre-metastatic niches, respectively, as well as a team comprised of leading pancreatic cancer clinical investigators including VHIO’s Teresa Macarulla, PI of our Gastrointestinal & Endocrine Tumors Group, and specialists in proteomics and biocomputing.

Based on the hypothesis that tumor cells use these micropeptides as cancer messengers inside exosomes, the investigator will strive to establish just how they promote cancer progression and disease spread towards developing novel therapies and ultimately improving outcomes for patients.

Marking World Cancer Research Day (WCRD), the Asociación Española Contra el Cáncer (Spanish Association against Cancer – AECC) announced its 2019 awardees during a special ceremony in Madrid presided by Her Majesty the Queen Letizia of Spain, its Honorary President, alongside Pedro Duque, Spanish Minister of Science, Innovation and Universities, and Ignacio Muñoz, AECC’s President.

VHIO’s Director, Josep Tabernero, presenting during the Asociación Española Contra el Cáncer (Spanish Association against Cancer – AECC) Annual Awards Ceremony 2019, celebrated on the occasion of World Cancer Research Day (WCRD), 24 September. This World Day was launched back in 2016 by AECC to encourage the active involvement of researchers, citizens, institutions and leaders across the globe to support the advancement of research against cancer.
Roundtable debate session during World Cancer Research Day 2019.

Among the many internationally renowned cancer scientists and clinical investigators who were invited to attend this auspicious occasion were VHIO’s Director, Josep Tabernero, who delivered a talk highlighting Europe’s dedicated efforts aimed at solving cancer sooner, followed by a roundtable debate which counted on the expertise of VHIO’s Joaquin Arribas, Co-Program Director of Preclinical & Translational Research and ICREA Research Professor, alongside Eva Ciruelos, President of SOLTI and Medical Oncologist at the 12 de Octubre Hospital in Madrid, Carmen Vela, Director of EUROFIN-INGENASA collaborative projects and Member of the EU’s Health and Food Mission, Javier Garcia, Founder of Columbus Venture Partners, and Cristóbal Belda, Sub-General Director of Evaluation and Research Funding, Carlos III Health Institute (ISCIII).

Elena Élez, Medical Oncologist and Clinical Investigator of our Gastrointestinal & Endocrine Tumors Group (PI:Teresa Macarulla), was among the Award recipients who received funding as an AECC Senior Clinician. This particular category provides experienced medical professionals in oncology with support to develop and consolidate research at the clinical level.

Elena’s awarded project will enable her to continue developing minimally and non-invasive approaches for the early detection and/or progression of colorectal cancer including the study of prognostic and predictive values of circulating tumor DNA (ctDNA in advanced disease. Given that cancer relapse and metastatic cell spread are responsible for between 50-70% of colorectal cancer mortality, the need to bring these exciting methods closer to the clinic is critical.

Miriam Sansó, Post-Doctoral Fellow of our Cancer Genomics Group directed by Ana Vivancos, received an AECC Investigator’s Award. These grants support postdoctoral talents to pursue their respective scientific careers towards establishing their own research lines. Miriam’s project will center on the comprehensive molecular profiling of multiple primary tumors in lung cancer patients to elucidate common genetic origins.

Around 12% of lung cancer patients at Vall d'Hebron suffer multiple primary tumors (MPTs). When a second tumor is diagnosed in a patient with a previous history of cancer, the challenge is to evaluate whether the second lesion is a metastasis of the first or a new primary tumor. The genomic analysis of different MPTs could identify possible coincident genetic alterations in these patients, and integrative analysis will aim at seeking out genomic signatures of MPT risk.

Under the same category of AECC Investigator, Post-Doctoral Fellow of our Stem Cells & Cancer Group, Isabel Puig, received renewed funding this year for her development of novel therapeutics against colon cancer recurrence. Almost 50% of patients with colorectal cancer will relapse with a new, more aggressive tumor which reduces the survival of these patients.

The group, directed by Héctor G. Palmer, has identified a subpopulation of drug-resistant slow-cycling cancer cells with enhanced capacity to reinitiate tumors thus being responsible for disease relapse. They have identified TET2 gene as a relevant factor for slow-cycling cancer cells survival, which could therefore serve as a potential drug-target for their elimination, and also shown that 5-hydroxymethylcytosine, generated by TET2 enzymatic activity, is a valuable biomarker to predict relapse in colorectal cancer patients.

Another VHIO project, awarded under the category of AECC Seed Ideas, is led by Pere Barba, Clinical Investigator of our Experimental Hematology Group directed by Francesc Bosch. His research will focus on optimizing checkpoint inhibitors to improve outcomes for patients with lymphoproliferative neoplasms who receive allogneneic hematopoietic cell transplantation (allo-HCT).

PD-1 inhibition could be damaging in patients who undergo stem cell transplantation, resulting in an increased risk of graft-versus-host disease and other immune-mediated complications. VHIO investigators will study PD-1 inhibitors in patients who have received a transplant and identify strategies to prevent damaging side effects in these patients.

VHIO would like to acknowledge AECC’s invaluable contribution to promoting cancer discovery and translational research of excellence, and the support it gives to countless researchers and groups across Spain and beyond.

Left to right: VHIO’s Josep Maria Miquel (Senior Project Manager), Elena Élez (Clinical Investigator & Medical Oncologist), Josep Tabernero (VHIO’s Director), Cristina Saura (PI: Breast Cancer & Melanoma Group), César Serrano (PI: Sarcoma Translational Research Group), Sandra Porta (Project Management Coordinator).

The third edition of the Catalonian Department of Health’s Strategic Plan for Research and Innovation in Health (Pla Estratègic de Recerca i Innovació en Salut, PERIS), announced 66 award recipients in 2019. The selected projects, recognized for their promise to yet further strengthen research throughout the region, are set to deliver on PERIS’ ambitions of promoting health and wellbeing among Catalonia’s citizens, increase international competitiveness to reaffirm the community as a leading hub of research and innovation of excellence, as well as further establish health as a key driver of social and economic development.

VHIO picked up recognitions in each of the three defined categories, namely, professional development, the incorporation of new research talents and technicians in existing groups, and support to drive and engage in international scientific activities.

First, PERIS funding will facilitate the recruitment of an additional group member which will enable Elena Élez (Clinical Investigator of our Gastrointestional & Endocrine Tumors Group), to dedicate the necessary time to implement and lead a project for detecting relapse in advanced colon cancer patients by longitudinally following a personalized molecular signature liquid biopsy.

Newly introduced this year, PERIS’ Go Europe grants award research support units of accredited research institutes and centers belonging to the CERCA Institute, in order to extend their global reach, increase participation in international projects -EU’s Horizon 2020 Research and Innovation programme in particular- as well as improve their success rate and returns achieved through competitive grants.

Specifically, this funding will strengthen VHIO’s international grant application processes and consolidate our European Projects Office directed by Alejandro Piris, Scientific Manager, VHIO’s Scientific Coordination Area.

Since it was established back in 2010, this specialized unit has evolved from an office providing basic support to a highly professional team with experience in both cancer research and project management. Go Europe support will further enable Alejandro’s department to centralize all identified proposals and projects presented by VHIO researchers and management teams, match them to existing and future calls across various funding sources, and tailor them to the requirements of the respective calls.

Regarding the incorporation of new research faculty and technicians in existing groups, Cristina Saura, Joaquin Mateo, and César Serrano, PIs of our Breast Cancer & Melanoma, Prostate Cancer Translational Research, and Sarcoma Translational Research Groups, respectively, also received funding to incorporate new talents within their teams.

Celebrating the 16th edition of the Fundación Mutua Madrileña’s Health Research Awards 2019, VHIO’s Maria Abad, Principal Investigator of our Cellular Plasticity & Cancer Group, was prized for her research to seek out micropeptides that are implicated in pancreatic cancer, and functionally characterize their role and relevance towards targeting these molecular messengers as markers of disease progression and metastases.

Recipients of the Fundación Mutua Madrileña’s Health Research Awards 2019.

Micropeptides are tiny proteins that, due to their size, have gone largely unnoticed under the lens. Up until now, that is. While the microproteome remains a relatively unexplored area, it is already showing promise in advancing discovery against cancer.

Out of the mere handful of micropeptides that have been characterized to-date, three have been linked to cancer. Considering that there are thousands of these micro proteins in our cells, it is plausible that many of them, yet to be discovered, could assume important roles in tumor formation and metastatic cell spread.

This support will further enable Maria Abad’s team to investigate the microproteome of pancreatic cancer and identify novel micropeptides that can be used as therapeutic targets as well as biomarkers of disease. They have previously unmasked several micropeptides implicated in cancer; some halt tumor growth, while others prevent cancer cells from invading other tissues and metastasizing. This funding will help the group to navigate this new world of micropeptides in greater depth toward translating their therapeutic promise at the clinical level.

Celebrated at the CaixaForum center for culture in Barcelona, the Fundación Internacional Dona Emprenedora (International Foundation for Women Entrepreneurs - FIDEM) announced the 2019 recipients of its annual prizes that honor exceptional examples of pioneering entrepreneurship led by women. Now in its 22nd edition, this recognition also applauds those companies and initiatives that spur economic development and promote societal enrichment.

The 2019 FIDEM Award winners at the ceremony hosted by CaixaForum.
Among the eight winners, who were each selected from a short list of five nominees/companies per category, VHIO’s Laura Soucek, Principal Investigator of our Mouse Models of Cancer Therapies Group and ICREA Research Professor, was prized under Innovation for her research centered on translating Omomyc-based therapy into clinical application, which subsequently led to the creation of a VHIO-born spin-off, Peptomyc S.L, back in 2014.

The la Fundació Catalunya La Pedrera (Catalunya la Pedrera Foundation) Pedrera Talents prizes launched in 2012 to recognize and promote the careers of young talents in healthcare who work at hospital across Catalonia.

In 2019, 20 prizes were awarded to young professionals who have completed their specialty training, to support their continued development at their respective hospitals or research centers as healthcare providers and researchers.

1- The 20 awardees of the 2019 Catalunya la Pedrera Foundation’s Pedrera Talents prizes. 2- VHIO’s Managing Director, Andrés de Kelety presents VHIO’s Iosune Baraibar with her Award certificate.

The ceremony counted on the official presence of panelists Lluis Farrés, Director of the Foundation’s Knowledge & Research Area, Anna Meseguer, Head of Operations & Institutional Relations of the Dirección General de Investigación e Innovación en Salut (General Direction of Health Research and Innovation), Jordi Ara, General Manager of the Instituto Calalán de la Salud (ICS) - Área Metropolitana Norte (Catalan Institute of Health – North Metropolitan Health Service), Josep Maria Campistol, Director General of the Hospital Clínic de Barcelona, and Andrés de Kelety, VHIO’s Managing Director.

Iosune Baraibar, the first to have received a Pedrera Talents Prize from VHIO, was awarded for her project Identification of response biomarkers to anti-TGFβ anti-LIF treatments in cancer patients. Iosune, a Clinical Investigator of our Gastrointestinal & Endorcine Tumors Group’s translational research program, directed by Teresa Macarulla, was also one of the six awardees who were selected to deliver a brief talk on her prized project-elevator pitch- during the event.

The Ceremony also included roundtable sessions; one of which, Women in Science, included Elena Garralda, Director of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, and PI of our Early Clinical Drug Development Group, as an Invited Speaker.

VHIO’s Elena Garralda as Invited Speaker of the round table session on Women in Science.

Thanks to the fundraising efforts of the 2018 annual telethon La Marató organized and led by media channels, TV3 and Catalunya Ràdio, dedicated that year to cancer research, seven VHIO-led projects, as well as one more in which VHIO will participate as a partner, were selected and prized this year.

Elena Élez, Medical Oncologist and Clinical Investigator of our Gastrointestinal & Endocrine Tumors Group, headed by Teresa Macarulla, will advance liquid biopsy as an approach to less invasively and more precisely track, monitor and evaluate individual patients suffering from colorectal cancer. She will seek to establish whether this technique can more effectively predict response to anti angiogenic therapies that can stop tumors from growing their own blood vessels, and thus slow and even shrink tumor growth.

VHIO’s recipients of La Marató funding awarded in 2019.

Violeta Serra, who directs VHIO’s Experimental Therapeutics Group, received Marató funding to investigate mechanisms of resistance to therapy with PARP inhibitors (PARPi). By liquid biopsy, Violeta’s team will aim to establish whether the RAD51 biomarker, that can predict sensitivity to PARPi, can more effectively identify the patients who will be most likely to benefit.

Raquel Perez-Lopez, Principal Investigator of Radiomics at VHIO, received funding to analyze the use of molecular diffusion nuclear magnetic resonance imaging in the monitoring of patients with bone metastases. This new approach might ultimately help to better guide treatment decision making and improve outcomes for patients – particularly those with advanced prostate and breast cancers.

Alena Gros, Principal Investigator of our Tumor Immunology & Immunotherapy Group was awarded for research centered on developing more effective and personalized immune-based therapies for the treatment of patients suffering from advanced endometrial carcinoma. This project will focus on the characterization of immune cells that reside in the tumors, the expansion of tumor-infiltrating lymphocytes (TIL) from tumors, and the development of mouse models of patients’ immune systems.

Laura Soucek, Principal Investigator of VHIO’s Mouse Models of Cancer Therapies Group and ICREA Research Professor, heads up research aimed at developing viable, non-toxic pharmacological options for Myc targeting in the clinic. Her group also received Marató funding to validate novel Omomyc-based cell penetrating peptides for cancer therapy.

Specifically, her group seeks to establish that Omomyc can put the brakes on tumor progression and achieve a change in the immunosuppressive tumor microenvironment and promote the immune control of tumors. They will also combine Omomyc with current immunotherapies to assess the potential efficacy of this therapeutic approach, as well as study the impact of MYC inhibition in KRAS-driven lung cancer, along with other mutations that inactivate tumor suppressor genes.

VHIO’s Francesc Bosch, Principal Investigator of Experimental Hematology, also received Marató funding to better understand the specific changes that promote the clinical progression of chronic lymphocytic leukemia (CLL) which leads to the decline in function of the immune system. These insights would help to more precisely predict the course of this disease.

Thanks to Marató funding this year, Sandra Peiró, who directs our Chromatin Dynamics in Cancer Group, will study cholangiocarcinoma; a less common yet difficult-to-treat tumor type, which is generally diagnosed at late stage with a high risk of recurrence after surgery. Sandra’s group will study the IDH1/2 mutation that is present in 20% of these tumors. This mutation generates an oncometabolite that alters the epigenetic pattern of mutated IDH1 cells. By better understanding the genetics and epigenetics of this disease, they hope to ultimately improve outcomes for patients.

In addition to these seven funded projects, Josep Villanueva, Principal Investigator of VHIO’s Tumor Biomarkers Group, will participate in a project coordinated by Virgina Amador, the August Pi Sunyer Institute for Biomedical Research (IDIBAPS) in Barcelona. The team will study the tumor immune microenvironment and the pathogenesis and control of mantle cell lymphoma (MCL). Josep will lead the research focused on the secretome of these tumors.


VHIO-organized events: sharing the latest insights & 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.

VHIO -”la Caixa” Scientific Seminars Series

Launched in 2019, our VHIO –”la Caixa” 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.

Taking place in VHIO’s state-of-the-art CELLEX Building Auditorium, each seminar 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 typically scheduled to take place on Fridays.

Scientific Co-Chairs: María Abad, PI, Cellular Plasticity & Cancer Group, Laura Soucek, PI, Mouse Models of Cancer Therapies Group, and Elena Élez, Medical Oncologist and Clinical Investigator, Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla, directed by Josep Tabernero).

Scientific Coordinator: Josep Maria Miquel, VHIO’s Project Manager (Scientific Coordination Area directed by Alejandro Piris, Scientific Manager).

Inaugural Seminar from left to right: Scientific Co-Chairs - Elena Élez, Maria Abad, Laura Soucek, Co-Host - Josep Villanueva, Invited Speaker - Ángela Nieto, and VHIO’s Director, Josep Tabernero.

Inaugural Seminar

Speaker: Ángela Nieto, Research Professor, Institute of Neurosciences, Miguel Hernández University (UMH) – Spanish National Research Council (CSIC).
Talk title: Epithelial plasticity in health and disease (the Ins and Outs of the EMT). Date: 20 September.
Co-hosts: VHIO’s Director Josep Tabernero & Josep Villanueva, PI of our Tumor Biomarkers Group.


VHIO-"la Caixa" Scientific Seminar Series 2019

Speaker: Antonio Maraver, Team Leader of the Oncogenic Pathways in Lung Cancer Group, Institute de Research en Cancérologie de Montpellier (ICRM), Montpellier, France.
Talk title: Role of the Notch pathway in lung adenocarcinoma: beyond the KrasG12V mouse model.
Date: 08 November.
Host: Maria Abad, PI, Cellular Plasticity & Cancer Group.


Speaker: Justin Odegaard, Vice President of Clinical Development, Guardant Health, Redwood City, California, USA.
Talk title: The current utility and future promise of liquid biopsy.
Date: 21 November.
Co-hosts: VHIO’s Director, Josep Tabernero, and Ana Vivancos, PI, Cancer Genomics Group.


Speaker: Julio Aguirre-Ghiso, Director of Head and Neck Cancer Basic Research, Director of Solid Tumor and Metastasis Research, Division of Hematology and Oncology, Department of Medicine and Otolaryngology, Mount Sinai School of Medicine, New York, USA.
Talk title: Role of adult stem cell niches and primed pluripotency programs in early DCC dormancy
Date: 28 November.
Host: Héctor G. Palmer, PI, Stem Cells & Cancer Group.


Speaker: Nuria López Bigas, Group Leader of the Biomedical Genomics Research Group, Institute for Research in Biomedicine Barcelona – IRB, Barcelona, Spain.
Talk title: Tumor genomes shed light on mutational processes and cancer vulnerabilities.
Date: 13 December.
Host: María Abad, PI, Cellular Plasticity & Cancer Group.


I-Mei Siu, Senior Editor of Cancer Discovery with our Director, Josep Tabernero, in front of VHIO’s CELLEX Center.

Building on the successes of our previous annual series of VHIO Meet the Editors, we continue to welcome the editors of some of the most prestigious journals within our field. In 2019, we had the pleasure of hosting I-Mei Siu, Senior Editor of Cancer Discovery, who met with our PIs, groups and research teams, and toured our state-of-the-art building – the CELLEX Center.





Ad-hoc courses, workshops & observerships

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 and hosted a total of 50 Courses, Workshops, Observerships and Perceptorships in 2019.

1. Preceptorship on Locally Advanced Melanoma, 31 January-01 February. Coordinator: Eva Muñoz Couselo. 2. Inmunoterapia y Tratamientos Dirigidos en Cáncer del Pulmón, 28 February – 01 March. Course Director: Enriqueta Felip. 3. Sharing Experiences: from Molecular Biology to Clinical Management, 09 -10 May. Director: Francesc Bosch. 4. II Reuniones Regionales de GIST, 16 May. Meeting Organizer: César Serrano. 5. Advanced Management of Gastroenteropancreatic Neuroendocrine Tumors, 16 – 17 May. Director: Josep Tabernero. 6. 14º Curs de Formació d’Assaigs Clínics en Oncologia i Hematologia, November. Organizer: VHIO’s Clinical Trials Office.

Our 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, they can also express their ideas surrounding a given topic presented at each seminar. The specially crafted informal format of these meetings favours free thought, flow, and interaction between the speakers and participants.

Current Benchstorming Co-Chairs, Elena Senís (left) and Chiara Bellio (right).

As the Benchstormings turned three years old in 2019, Elena Senís, Post-Doctoral Fellow of VHIO’s Cellular Plasticity & Cancer Group (PI: Maria Abad) and Benchstorming Co-Chair, announced that Chiara Bellio, Post-Doctoral Fellow of VHIO’s Tumor Biomarkers Group (PI: Josep Villanueva), had taken over the reins from previous Co-Chair Toni Jauset, formerly a graduate student of VHIO’s Mouse Models of Cancer Therapies Group and researcher at VHIO-born spin-off Peptomyc S.L. We take this opportunity to thank Toni for his hard work and dedication.

In 2019, they organized 16 Benchstorming Sessions during which researchers discussed and ‘benchstormed’ their research areas. Each session is graded by all attendees and one presenter is announced as winner of the best presentation for each season.

Faiz Bilal, Post-Doctoral Fellow of our Growth Factors Group (PI: Joaquín Arribas), was announced as the best presenter for January-June’s series for his talk on Overcoming resistance to targeted therapies in MAPK dependent tumors.
Andrea García, Graduate Student, VHIO’s Tumor Immunology & Immunotherapy Group (PI: Alena Gros), was announced as the winner of the September-December series for her talk on Development of personalized minimally-invasive T-cell therapies targeting the tumor mutanome.

Building on the success of the ‘spin-off’ Techstorming sessions to present on novel technologies and latest lab approaches in cancer research, Elena and Chiara introduced an additional sister Benchstorming series with especially paired preclinical-clinical expert sessions on a selected hot topic.

Elena Élez, Medical Oncologist and Clinical Investigator of our Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla, Director: Josep Tabernero), joined together with Laura Escudero, Post-Doctoral Fellow of VHIO’s Gene Expression & Cancer Group (PI: Joan Seoane), to present on Liquid Biopsy. Irene Rius, Post-Doctoral Fellow of our Growth Factors Group (PI: Joaquín Arribas), and Pere Barba, Hematologist and Clinical Investigator of Experimental Hematology (PI: Francesc Bosch), reported on CAR T-cells. Tackling the topic of Immunotherapy were Elena Garralda, PI of VHIO’s Early Clinical Drug Development and Director of our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, and Andrea García, Graduate Student of VHIO’s Tumor Immunology & Immunotherapy Group (PI: Alena Gros).

We also take this opportunity to highlight a special session presented by Marie-Eve Beaulieu, Co-Founder & CSO, of VHIO-born spin-off, Peptomyc S.L., Alba Llop, Leader of VHIO’s RAD51 predict test project and Post-Doctoral Fellow of VHIO’s Experimental Therapeutics Group (PI: Violeta Serra), and Carlos López, Business Development Manager at VHIO (Scientific Coordination Area directed by Alejandro Piris, Scientific Manager), entitled Bringing your great ideas to market.


VHIO's public engagement & outreach

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. We will continue to identify, lead and participate in all these precious initiatives and launch new ones based on identified opportunities.

In 2019, VHIO led and/or participated in over 40 public outreach events, programs and fundraising initiatives including:

  • II Reunión Regional de GIST (II Regional GIST Meeting)
  • 48H Open House BCN – open days for the general public.
  • III Mocador Solidari presentation
  • Spanish Association against Cancer (AECC) conference:
  • El tumor cerebral: una visión integral - An integral vision of brain cancer
  • Carrera por el Càncer de Páncreas - runathon to support research against pancreatic cancer
  • Jarabe y amigos contra el cáncer - Pau Donés’ cancer research fundraising rock concerts
  • El Paseico de la mama – strollathon for breast cancer
  • Festival de la Ciencia (Science Festival)
  • Festival de cine de Alicante (Alicante Film Festival) - Dones en Actiu
  • Marnaton 4 FERO – swimathon organized by the FERO Foundation
  • Pink Run Mir – runathon fundraiser for breast cancer research
  • Una palabra. Una Mujer. Una vida - exhibition and workshop dedicated to raising awareness about breast cancer
  • The Youth Mobile Festival: YoMo
  • VHIO’s Escuela y Ciencia Program - see sub-section
  • VHIO-HUVH’s annual series of workshops for patients suffering from breast cancer
  • II VHIO-IDIBELL-ICO Workshop on Prostate Cancer
  • VHIO’s Running for Research (R4R) – in collaboration with the FERO Foundation - see sub-section
  • MBA BCN Global - student visits to VHIO
  • Visit by Portugal's Minister for Science, Technology and Higher Education, Manuel V. Heitor
  • Visit to the Escuela de Administración Pública de Catalunya AC Montcada
  • Visit to the Escuela Virolai
  • ProstateNet Workshop
  • World Cancer Research Day institutional presentation & open meeting
  • Zumba Solidario – Zumba workouts to support research against cancer


In 2019 VHIO’s education program, Schools and Science, welcomed a total of over 490 under-twelves from 6 local primary schools to meet our faculty, tour our laboratories and learn more about cancer biology and research.

The main objectives of this outreach program are to teach young and inquisitive minds about the importance of research in solving cancer sooner, how we at VHIO conduct our investigation, and to hopefully inspire some to ultimately become the next generation of cancer scientists.

During their half day visits our young visitors participated in junior masterclasses and hands-on activities to explain the origins and development of cancer, led and supervised by VHIO faculty. In view of the tremendous success and excellent feedback received from the students and teachers, 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 2020.


Inspired by Daniel Massó Vallés, formerly a Postdoc of our Mouse Models of Cancer Therapies Group, and now researcher of VHIO spin-off Peptomyc S.L., and Irene Rius, Post-Doctoral Fellow of our Growth Factors Groups, VHIO’s Running for Research (R4R) currently comprises a team of some 20 researchers who are participating in several half and full marathons to mix and mingle with the general public and spread the word about who we are, what we do, and promote the value and importance of supporting cancer research.

Our dedicated runners, who officially enter sports events in the name of VHIO, are kitted out with R4R-branded baseball caps and t-shirts to increase visibility and trigger conversation with fellow runners and other members of the public present.

R4R participated in several ‘runathons’ in 2019, including the 5K and 10K races of the third annual Barcelona-based fundraiser of the Spanish Association against Cancer’s (AECC), Run against Cancer, Move for Multiple Sclerosis - the Granollers half marathon, the Barcelona marathon, the 5k Carrera de las Ciudades against Pancreatic Cancer, and the 12.5K Portlligat trail.

VHIO’s R4R rallying for research against cancer: 1- At the Spanish Association against Cancer’s (AECC) Run against Cancer. 2- The Carrera de las Ciudades to support research against pancreatic cancer. 3- Participating at the mountain race Portlligat trail.

One of our Institutional Supporters and Patrons, the FERO Foundation also promotes the importance of cancer research through the organization of several public engagement and annual fundraising initiatives and events.

As examples in 2019, it organized a ‘swimathon’, Marnaton 4 FERO, to raise money for research led by Héctor G. Palmer (PI of VHIO’s Stem Cells & Cancer Group) into the early detection of cancer recurrence by liquid biopsy.

Another FERO crowdfunding initiative surrounded its participation at the 41st Zurich Marató Barcelona, which also counted on several runners from VHIO’s Running for Research team. Funds raised were allocated to support molecular diagnostics at VHIO to help extend the more precise characterization of individual tumors and matching of anti-cancer therapies to an increasing number of patients.

Marnaton 4 FERO, Cadaqués (Girona, Barcelona).

VHIO’s Twitter account launched at the end of January 2019 and has since attracted over 3000 followers. To discover what we are excited about, our latest news, and other tweets that are catching our attention elsewhere, we invite you to follow us @VHIO and join the conversation today.


Celebrating its second birthday in December 2019, Wren’s Lens, our internal monthly newsletter, was devised to update all VHIO faculty on highlights covered in our news and/or media program along with special newsletter extras: Talent Tidbits, special features and dates in the diary that might be of interest.

The branding, inspired by our Communications Director’s surname, incorporates a silhouette of the Wren species perched on top of a lens accentuating VHIO’s logo. Reflective of its popularity and keen VHIO following, Wren’s Lens has since become more of an internal blog spot than a ‘news desk’ update.