The next decade of VHIO's translation toward precision oncology

Foreword

VHIO in 3 Words: Predictive, Proven & Precise

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

During the 2017 Congress of the European Society for Medical Oncology (ESMO), themed Integrating science into oncology for a better patient outcome, I was honoured to deliver a keynote address tackling the pressing issue of how to cope with escalating healthcare costs in cancer. Framed on the fable of the hare and the tortoise, I concluded that the entire oncology ecosystem should better combine the alacrity of the former and the deliberate progress of the latter to achieve optimal outcomes.

I believe that accelerating our efforts to advance our field must be based on careful, scrupulous evidence-based assessment and proven benefit for patients to ensure the best possible outcomes.

This cross-balance approach, emphasizing realistic yet pioneering strategic direction, has successfully established VHIO as a leading comprehensive cancer center on the global oncology stage. Last year's report celebrated our Institute turning ten. As we embrace the next exciting decade, I want to highlight just some of our many milestones throughout VHIO's brief history.

These important steps have all contributed to firmly positioning VHIO's 3 Ps - Predictive, Proven & Precise – at the core of our multidisciplinary and translational research model. Following these guiding principles, I highlight below some of the exceptional research advances, contributions and developments that have been driven by out talents and teams throughout 2017.

The science that shaped our year

As we embark on the next decade of VHIO's purely translational story, I am proud to report that 2017 was a record breaker in both the number and impact of papers published. Last year, 282 scientific articles were published by VHIO researchers as corresponding/senior or co-authors. Many appeared in prestigious international journals, others in more specialized publications, but I have never been prouder of the quality and scope of our research productivity.

These papers present myriad contributions to cancer science in preclinical, translational and clinical areas. It is impossible to showcase a representative selection here in my Foreword. That said, I take this opportunity to mention a mere few VHIO ‘hot spots’ that made the headlines throughout 2017:

Preclinical predictability

The issue of reproducibility of predictive preclinical science has been widely debated in the literature. 2017 kicked-off with a study (1) first authored by D. Benjamin, Biomedical Ethics Unit/STREAM, McGill University (Montreal, Canada), claiming that cancer researchers overestimate the reproducibility of their preclinical findings.

Whether one agrees with their arguments or not, we at VHIO strive to deliver the data required to reliably inform the clinical development of innovative agents and approaches before moving to the clinic. Reflective of our expertise in developing and tuning cancer models to identify factors influencing tumor growth, progression and response to therapy, VHIO is a founding member of the EuroPDX Consortium.

In a 2017 Perspectives article (2) EurOPDX members and co-authors explored the challenges of patient-derived xenografts (PDX), at the vanguard of precision medicine. In their elegant review of where we stand with these models in more faithfully recapitulating the molecular specificities of patient samples, the authors balance preclinical realities with current expectations from the clinical perspective.

Lastly, following their review of using next-generation models to establish the role of the immune system in tumor cell spread and test-bed the increasing portfolio of immunotherapeutics, one major ‘take home’ touched on the absolute necessity of sharing and exchanging data from various experimental models – a guiding principle that defines both the EurOPDX Consortium and VHIO.

Co-authored by VHIO's Paulo Nuciforo, Principal Investigator of our Molecular Oncology Group, a report (3) led by colleagues at the Dana-Farber Cancer Center, Boston (USA), in collaboration with VHIO researchers and the Medical Oncology and Pathology Departments of our Hospital, headed by myself and Santiago Ramón y Cajal respectively, showed that the colonization of human colorectal cancer (CRC) with Fusobacterium and its associated microbiome is found in primary tumors and persists in liver metastases.

Supporting the hypothesis that Fusobacterium travels with primary cancer cells as part of metastatic tissue colonization, findings also revealed that it survives through the multiple generation of PDX and that treating mice bearing bacterium-positive models with metronidazole significantly decreases tumor growth. These observations suggest that this bacterium is more than a mere bystander of tumorigenesis. It could in fact be a driver of metastases and selective antimicrobial therapy could therefore represent important weaponry for the treatment of patients with Fusobacterium-associated CRC.

Worthy of mention here is that VHIO's robust preclinical and translational research of excellence also spurred the creation of two successful spin-offs in 2014, both of which continue to go from strength to strength.

Championing combinations to improve response and halt metastatic spread

In an open access article (4), findings reported by a purely VHIO tour de force, first authored by Alex Martínez, Medical Oncologist and Clinical Investigator of VHIO's Thoracic Tumors & Head and Neck Cancer Group, directed by Enriqueta Felip, identified a novel and more effective therapeutic strategy to combat acquired resistance to third-generation epidermal growth factor tyrosine kinase inhibitor (EGFR-TKIs), osimertinib, in the treatment of metastatic non-small cell lung cancer (NSCLC).

Using a patient-derived orthopatic xenograft model, the team successfully characterized the role of MET gene amplification and signalling as a mechanism of resistance to osimertinib and showed the superior efficacy of pairing the EGFR inhibitor afatinib with a c-MET inhibitor, capmatinib. Further studies will explore the EGFR-TKI-MET inhibitor combination as a novel therapy, as well as consider the addition of immunotherapy for the earlier treatment of patients.

Presented for the first time during ESMO's 2017 Congress, Cristina Saura, Principal Investigator of VHIO's Breast Cancer Group, delivered results from the LORELEI phase II study. Assessing the efficacy of adding taselisib to letrozole before surgery for the treatment of patients with operable early estrogen receptor-positive and HER2-negative breast cancer, this study is the first to demonstrate a marked increase in response to treatment with a PI3K-selective inhibitor.

Carried out in collaboration with academic partners including the Breast International Group (BIG), SOLTI Breast Cancer Research Group, and the Austrian Breast & Colorectal Cancer Study Group (ABCSG), this research showed that taselisib and letrozole prior to surgery significantly improved outcomes for these patients compared to treatment with letrozole alone.

Results from another study (5), timed to coincide with this year's Annual Meeting of the American Association for Cancer Research (AACR), showed the promise of combining encorafenib with cetuximab, with or without alpelisib as a strategy against metastatic BRAF-mutant metastatic colorectal cancer (mCRC).

Both pairings demonstrated efficacy and acceptable safety profiles, with similar overall response rates: 19% in the dual and 18% in the triple combination group. In our efforts to suppress MAPK signalling and halt tumor growth in this difficult-to-treat population, these findings promise a new therapeutic avenue towards improving outcomes for patients.

VHIO's pursuit of new emerging research areas

In last year's Scientific Report I hailed the arrival of Sandra Peiró, Principal Investigator of VHIO's Chromatin Dynamics in Cancer Group, and Leticia de Mattos-Arruda, Junior Principal Investigator of Applied Genetics of Metastatic Cancer.

Throughout 2017, Sandra has successfully consolidated her lab. Her group elucidates the epigenetic mechanisms controlling the expression of genes during tumor progression, with special emphasis on the role of the primary structure of chromatin fiber, as determined by histone tail modification, and the 3D chromatin structure implicated in transcription regulation. By identifying the molecular mechanisms of chromatin conformation changes in tumor cells they strive to unveil potentially druggable proteins.

Leticia's research centers on integrating multi-omics data towards better understanding of tumor heterogeneity and the role of the immune system within and between tumors. She also focuses on identifying novel biomarkers to guide the selection of anti-cancer therapies based on the specificities of individual patients and advance insights into differential clinical responses in individuals with metastatic breast cancer.

At the end of 2017 we also warmly welcomed two new talents to VHIO whom we have lured from London:

Raquel Perez-Lopez moved to VHIO in October from the Institute of Cancer Research - Royal Marsden Hospital, where she conducted her PhD under the supervision of Johann de Bono, to head up our newly established Radiomics Group.

As Principal Investigator, Raquel's research will center on functional CT and MRI techniques such as perfusion, diffusion and spectroscopy, to better identify the histological and molecular characteristics of tumors. Her group will seek to optimize drug development by more effectively characterizing the antitumor effect of novel agents including immunotherapies, identify those patients who are most likely to benefit from these therapies, and further enforce our translational research programs in genomics, predictive science, and biomarkers of response and resistance.

Raquel has already established interdisciplinary collaborations with various VHIO groups, and soon she will welcome an MR researcher for novel imaging biomarker development and an MSc student and clinical research fellow on her team.

Also joining us from the same institution (and mentorship) is Joaquin Mateo, as Principal Investigator of our recently created Prostate Cancer Translational Research Group.

He will lead research aimed at translating prostate cancer genotypes into phenotypes and a clinically-relevant classification of the disease, and will also build a precision medicine core for prostate cancer patients. He has already recruited three group members to join us early next in 2018, and, together with our Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group, led by Joan Carles, has launched a program to prospectively acquire samples from metastatic lesions and circulating biomarkers from patients with metastatic prostate cancer treated at our hospital, the Vall d'Hebron University Hospital (HUVH).

These important additions will fortify VHIO as it continues to more swiftly translate cancer discovery into clinical benefit. To discover more about our recently incorporated groups click here.

Potentiating novel immune agents as mono therapy or in combination

It's not so long ago that immunotherapy featured in my Foreword as “emerging” or even promising but not as proven. At the close of 2017, Nature published its annual cherry-pick of bright spots (6) in science. The selection included the first approval of CAR-T cell therapy involving the genetic engineering of a patient's immune cells to target and attack tumors. The US Food and Drug Administration approved it for the use in children and young adults with a type of acute leukaemia.

Despite safety concerns regarding this treatment, we are seeing how the efficacy of novel immunotherapeutics is increasingly reported as proven, as opposed to merely promising, across different tumor types either as mono therapy or in combination. While the advent of immune-based therapies must be celebrated, their power and potential continues to vary immensely in patients. This is because some tumors manage to block the immune system defence or even sneakily slip past undetected.

Looking ahead, much research needs to center on better predicting response to these therapies in individual patients and thus further validate precision medicine in oncology. Only then can we reasonably expect to extend immunotherapies to more tumor types, as well as continue to combine powerful immunotherapeutics with the current cornerstones of cancer – chemotherapy, surgery and radiation. We will also need to better understand the cellular and molecular mechanisms modulating immune response as well as learn from the outcomes of current and future trials.

Announced in December, VHIO and the BBVA Foundation paired in collaboration with the Memorial Sloan Kettering Cancer Cancer Center – MSKCC (New York) to pioneer a Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI). Building on the successes of a previous joint project to implement a tumor biomarkers research program, 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.

This project will combine the expertise of VHIO's Elena Garralda (PI of VHIO's Early Clinical Drug Development and Executive Director of our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”), who will head up CAIMI's clinical research, Alena Gros (PI, VHIO's Tumor Immunology and Immunotherapy Group), who will take the lead on translational research, and Ana Vivancos(PI of our Cancer Genomics Group), who directs our internationally recognized pre-screening platform. In collaboration with our MSKCC colleagues, VHIO will co-found six translational projects linked to the early clinical development phases of immunotherapy.

Elsewhere, also reflective of VHIO's efforts aimed at accelerating immunotherapies including atezolizumab, nivolumab and pembrolizumab, results from two VHIO-led studies were selected for prestigious oral presentations during the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Enriqueta Felip revealed results from an early phase I multi-center trial designed to analyze the safety and dose escalation of the combination of ceritinib with PD-1 inhibitor nivolumab in patients with advanced ALK+ non-small-cell lung cancer.

While findings showed that ceritinib paired with nivolumab as active in these patients, considerable toxicity was observed, calling for adjustments of the protocol on the administration of this particular combination with an alternative dosage regimen in trials to follow.

During the meeting, I presented results from two early phase studies exploring the preliminary therapeutic activity and safety of the novel carcinoembryonic antigen (CEA) T-cell bispecific antibody, either as monotherapy or in combination with PD-L1 inhibitor atezolizumab in patients with mCRC.

We reported that when CEA is administered as monotherapy, an initial response is noted, yet, at the same time, it starts to express PD-1 /PD-L1 rendering the immune system dormant, leading to disease progression. When this agent is delivered in combination with the PD-1 /PD-L1 inhibitor however, there is a rating of 82% in response and stabilization of disease.

Ongoing studies will continue to validate this combinatorial approach, but these initial findings certainly show promise in boosting the immune system to mount an effective antitumor response against mCRC.

Big Data-derived insights and the pan-omic exploration of solid tumors

An additional framework agreement between VHIO and MSKCC, renewed this year, is the Obra Social ”la Caixa” 2nd International Program for Cancer Research and Education. This 3-year project will include several initiatives focused on the pan-omic exploration (genomics and radiomics) of solid tumors, with particular emphasis on Big Data. More specifically, with José Baselga, Physician-in-Chief at MSKCC and myself as co-PIs (in collaboration with Maurizio Scaltriti, MSKCC, and VHIO's Rodrigo Dienstmann, Ana Vivancos, Joaquin Mateo and Raquel Perez-Lopez) we will conduct research on the impact of gene mutations in DNA damage repair and metastatic prostate cancer, together with data mining to reveal new molecular genetic determinants of sensitivity to targeted therapy in solid cancers.

Talking of Big Data, VHIO also leads efforts to report, interpret and exchange meaningful mass data. Our Oncology Data Science (ODysSey) Group directed by Rodrigo Dienstmann, facilitates data exchange among a wide range of experts for the review of patient medical histories and cancer molecular profiles in order to guide treatment decisions.

As a partner of the EU Horizon 2020-funded MedBioinformatics, Rodrigo's group has been extensively involved in the development of integrative bioinformatics tools to analyze the huge amount of data and knowledge generated in healthcare and biomedical research in order to advance translational research. Furthermore, important advances in datamining and interpretation of somatic gene alterations with a therapeutic impact in cancer have spurred the development of the publicly available Cancer bioMarkers database, which has become a reference for clinical investigators across the globe.

Rodrigo's group, in collaboration with our Molecular Oncology and Cancer Genomics labs, led by Paolo Nuciforo and Ana Vivancos respectively, continues to focus on the multi-molecular approach to developing novel anti-cancer therapies based on established subtypes. As a result of our expertise in cancer classification, this year we published a review article (7) underlining the challenges and opportunities ahead in putting the brakes on the molecular culprits that drive tumor initiation, development and growth in each individual consensus molecular subtype of colorectal cancer.

Representing an important forward step in this direction, as this Report goes to print, I am proud to announce that VHIO has been accepted as a new participant in the AACR international data-sharing initiative known as AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), launched back in 2015.

It's not just about consensus in the subtyping, it's also about harmonizing the same language in oncology, precisely speaking! Aimed at resolving certain ambiguity arising within the oncology community concerning terminology entering the cancer lexicon, ESMO's Precision Medicine Glossary (8) incorporates 43 selected terms that, upon consensus, were grouped across 5 main categories: mechanism of decision, characteristics of molecular alterations, tumor characteristics, clinical trials & statistics, and new research tools. Also tackling the ‘which is best’ debate on precision as opposed to personalized, this glossary is a useful tool to improve communication and thus further spur collaborative research of excellence.

Liquid biopsy: better guiding treatment decisions for our patients

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

As a direct reflection of our expertise in developing this approach at clinical level, driven in collaboration with our Cancer Genomics Group, VHIO counted two out of the five projects selected under the TRANSCAN Joint Translational Call on Minimally and non-invasive methods for early detection and/or progression of cancer.

Awarded by the Spanish Association against Cancer (AECC) and the Institute of Health Carlos III (ISCIII) through the ERA-NET TRANSCAN-2 program funded by EU's Horizon 2020, the first of VHIO's two TRANSCANs, led by Enriqueta Felip, Principal Investigator of our VHIO's Thoracic Tumors & Head and Neck Cancer Group, will establish non-invasive prognostic markers for resected early stage non-small cell lung cancer (NSCLC) by assessing the role of circulating and exosomal miRNAs and free circulating DNA (fcDNA).

The second, directed by Elena Élez, Medical Oncologist and Clinical Investigator of VHIO's Gastrointestinal & Endocrine Tumors Group, focuses on the early detection of relapse in advanced colon cancer patients by longitudinally following a personalized molecular signature by liquid biopsy. This proof-of-concept, prospective and multi-center study seeks to evaluate the clinical feasibility of tracking tumor progression by dynamically detecting a molecular signature from a blood test. As an innovative approach for the early detection of disease relapse, this project represents an important next step in more accurately monitoring cancer's next moves.

Task-forcing team science

VHIO's expert and interdisciplinary taskforces comprise comprehensive teams of oncologists, pathologists, other MD disciplines, preclinical and translational researchers, research nurses, data curators and miners as well as study coordinators, among others.

Currently counting seven groups covering colorectal, breast, lung, gynecologic, prostate, melanoma tumor types as well as immunotherapy, our taskforces regularly convene to synergize efforts, boost collaborations among groups and between specialists, and continuously revise respective circuits and ethics toward advancing cancer science and medicine.

In line with recommendations outlined in our Scientific Advisory Board's 2017 Report, and to complement and expand our priority research areas, we will seek to further develop and functionalize our appointed taskforces as well as strengthen our shared and standard operating procedures.

Picking up the prizes and A-grade accreditation

In recognition of VHIO's efforts aimed at rendering cancer medicines more precise and our contribution to the Spanish National Health System, we received Gaceta Médica's 2017 Best-in-Class Prize for R&D in oncology.

Based on our ability to advance cancer discovery through the integration of translational science and clinical research, this wonderful accolade also recognizes the work performed at the hub of VHIO's early drug development program led by Elena Garralda, our Research Unit for Molecular Therapies of Cancer (UITM) – ”la Caixa” (click here).

More specifically, the Unit's broad portfolio of promising novel anti-cancer therapies continues to grow each year with special focus on first-in-human studies, novel combinations, and best-in-class compounds. Since its inauguration in 2010, the UITM, previously coordinated by Jordi Rodón and now under the direction of Elena, has established itself as one of the few comprehensive facilities in Europe to up the tempo in transforming latest discovery into benefits for our patients.

Launched this year, the European Alliance for Personalised Medicine's (EAPM) Health Innovation Five ‘HI-5' Award for the Best EU-based hospital for integrating personalised cancer medicines was presented to VHIO in recognition of our capacity to swiftly integrate and transform precision medicine against cancer.

At the core of everything we do, our rapid translation of cancer discovery into benefits for patients is only possible thanks to VHIO's multidisciplinary teams composed of research talents, top drawer clinical investigators, leading physicians, expert oncology care providers at our Hospital's Medical Oncology Department, in collaboration with other healthcare professionals across the Vall d'Hebron Barcelona Hospital Campus.

Additionally in 2017, VHIO underwent evaluation for accreditation of the CERCA Institute of Research Centres of Catalonia (Institució CERCA – Centres de Recerca de Catalunya) for the period 2013 – 2016. In recognition of VHIO's progress, performance in knowledge transfer activities and management of excellence, VHIO was awarded with the maximum qualification of an A grading.

The Last Word

“People do not decide to become extraordinary, they decide to accomplish extraordinary things.”
- Sir Edmund Hillary, Explorer (1919–2008)

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 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, FERO Fundación de Investigación Oncológica, Fundació Bancària la Caixa”, Fundación BBVA, as well as VHIO's many other supporters, funding entities and agencies (click here).

We can and will only continue to accelerate our pace in advancing more precise, effective and targeted therapies against cancer through the public funding we receive, as well as the generous support from private institutions, companies and individuals, all of whom share the same intense desire as we do: to reduce the devastating burden that this disease has on society.

In 2015 there were an estimated 17.5 million cancer cases globally, with 8.7 million deaths. Cases are forecast to soar by 75% over the next 20 years. Added to this alarming picture, spending on cancer medicines totaled $107 billion worldwide in 2015 and is projected to exceed $150 billion by 2020 (9). This tremendous socioeconomic burden on healthcare systems across the globe can no longer be sustained anywhere – irrespective of national cancer plans, allocated resources or corresponding treasury.

Driving advances in cancer discovery and translating these insights into improved outcomes for patients as quickly as possible must therefore be a top priority for the entire oncology ecosystem as well as the public at large, globally.

As I close this Foreword and consider the many vital contributions that VHIO's teams make to cancer science and medicine, I am proud to report that we are getting smarter and moving faster in our quest to combat cancer.

Building on the progress made over VHIO's first decade, we are more committed than ever to expanding our efforts in breadth, depth, and scope – faithful to VHIO's 3 established principles: Predictive, Proven & Precise.

As VHIO evolves in tune with the current era of precision medicine, we can and will do better.

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


References:

  1. Benjamin D, Mandel DR, Kimmelman J. Can cancer researchers accurately judge whether preclinical reports will reproduce? PLoS Biol. 2017 Jun 29;15(6):e2002212.
  2. Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinská E, Caldas C, Chang DK, Clarke RB, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek MA, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer HG, Peeper DS, Pelicci PG, Piris-Gimenez A, Roman-Roman S, Rueda OM, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Apr;17(4):254-268.
  3. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017 Dec 15;358(6369):1443-1448.
  4. Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel JM, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer HG, Vivancos A. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017 Oct 1;28(10):2451-2457.
  5. van Geel RM, Tabernero J, Elez E, Bendell JC, Spreafico A, Schuler M, Yoshino T, Delord JP, Yamada Y, Lolkema M, Faris JE, Eskens FA, Sharma S, Yaeger R, Lenz HJ, Wainberg ZA, Avsar E, Chatterjee A, Jaeger S, Tan E, Maharry K, Demuth T, Schellens JHM. A phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. 2017. Cancer Discov. 7: 610-619.
  6. Callaway E, Castelvecchi D, Cyranoski D, Gibney E, Ledford H, Lee JJ, Morello L, Phillips N, Schiermeier Q, Tollefson J, Van Noorden R, Witze A. 2017 in news: The science events that shaped the year. Nature. 2017 Dec 21;552(7685):304-307.
  7. Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 2017;7(2):79-92.
  8. Yates LR, Seoane J, Le Tourneau C, Siu LL, Marais R, Michiels S, Soria JC, Campbell P, Normanno N, Scarpa A, Reis-Filho JS, Rodon J, Swanton C, Andre F. The European Society for Medical Oncology (ESMO) Precision Medicine Glossary. Ann Oncol. 2018 Jan 1;29(1):30-35. (13 November, epub ahead of print).
  9. IMS Institute for Healthcare Informatics. Global Oncology Trend Report: A Review of 2015 and Outlook to 2020. June 2016.


2017: marking the next chapter of VHIO’s translational story

Who we are and what we do

VHIO's Organigram 2017

In order to translate cancer discovery into real benefit for an increasing number patients, VHIO has, for the last decade, adopted a purely translational, multidisciplinary research model. Organized into four 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:

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VHIO's translation toward precision oncology: a little more on how we did it in 2017

Under the leadership of Josep Tabernero, the Vall d'Hebron Institute of Oncology (VHIO), created by José Baselga in 2006, has established itself as a comprehensive cancer centre of proven excellence internationally. It is thanks to exceptional directorship and VHIO's optimal organizational structure based on a purely multidisciplinary and translational model that VHIO talents continue to anticipate and tackle the many unresolved questions in combatting this multifaceted and heterogeneous disease.

Located within the Vall d'Hebron Barcelona Hospital Campus, our researchers closely collaborate and interact with Vall d'Hebron University Hospital 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.

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Principal areas of cancer research at VHIO: a snapshot

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

Prowess in prescreening and oncogenomics

At the core of VHIO's research activities lies 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 to bridge the preclinical and clinical levels of cancer discovery.

VHIO's Prescreening Program, pioneered by VHIO's Cancer Genomics Group and Molecular Oncology Group led by Paulo Nuciforo, performs molecular profiling in over 1500 patients per year as candidates for enrollment in Phase I clinical trials carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Jordi Rodón. Suitability for enrollment in a given trial is evaluated based on the genomic or pathologic profile of individual patients. Our capacity to more precisely match individual patients with a particular clinical study represents a significant forward step in the collective and collaborative ambition to deliver on the true promise of personalized treatment and care in oncology.

As a reflection of our dedication to excellence and quality services we provide, we continue to undergo ISO 15189 accreditation for our main testing methods and our prescreening efforts have already established VHIO as one of the few centers in Europe to run such a comprehensive program. We will continue to expand our efforts to an increasing number of patients thanks to the VHIO - Catalan Institute of Oncology (ICO) Research Alliance, representing the biggest clinical care provider in Catalonia.

As updated by our Director in his Foreword, in collaboration with Merck Serono and Sysmex Inostics, we continue to employ our in-house Digital-PCR Platform, BEAMING liquid biopsy RAS biomarker technology, for the detection of RAS mutations in first-line metastatic colorectal cancer.

While we are already seeing how this avant-garde approach is promising a more precise treatment for metastatic colorectal cancer patients by improved stratification of which patients stand to benefit from anti-EGFR therapies, we will aim to further develop and empower this technology towards its application to conventional care across an increasing number of tumor types.

By bringing more detailed prognostics directly to the clinical setting, and further developing and validating the next generation of tests, VHIO continues to significantly contribute to better guided treatment decisions as well as improved outcomes for patients.

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Technologies in Cancer Genomics: an ongoing revolution.

Our state-of-the-art enabling technologies include an n-counter Nanostring platform, BEAMing Sysmex, and Droplet Digital PCR (ddpCR) Bio-Rad Technology, Miseq and HiSeq2500, Illumina.Two of these tests are based on NGS: an Amplicon-seq approach to sequence 70 genes (Illumina), as well as a 400-gene capture panel, and two are based on nCounter (Nanostring): a gene fusion panel (with the capacity of detecting over 100 recurrent gene fusions) and a Copy Number Alteration panel (detecting 59 genes).

As a reflection of high quality testing on patient samples, VHIO is increasingly approached by the pharmaceutical industry and other research entities as either the selected Central Lab of choice, or as their preferred service provider and advisor.

VHIO's Prescreening Program, pioneered by VHIO's Cancer Genomics and Molecular Oncology Groups (led by Ana Vivancos and Paolo Nuciforo respectively), performs molecular profiling in over 1500 patients per year as candidates for enrolment in early phase clinical trials carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Elena Garralda.

Suitability for enrolment in a given trial is evaluated based on the genomic or pathologic profile of individual patients. Our capacity to more precisely match individual patients with a particular clinical study represents a significant forward step in delivering on the true promise of personalized treatment and care in oncology.

By bringing more detailed prognostics directly to the clinical setting, and further developing and validating the next generation of tests, VHIO also continues to significantly contribute to better guided treatment decisions as well as improved outcomes for patients.

As a reflection of our dedication to excellence and quality services we provide, we continue to successfully undergo ISO 15189 accreditation and are now focused on transferring some of our technologies.

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

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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 (click here), under the direction of Josep Tabernero and now coordinated by Elena Garralda as Executive Director, 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 (click here), and focuses on the development of novel agents based on the molecular profile of each tumor as well as the optimization of therapies using combinations of new drugs with existing ones.

In 2017, 120 Phase I clinical trials and 17 basket studies were performed at our Unit with a total of 445 patients enrolled. Our Clinical Trials Office (click here), directed by Gemma Sala and also located in the patient environment of the Vall d'Hebron University Hospital, coordinates a large portfolio of Phase I, Baskets, Phase II & III clinical trials. In 2017 the number of patients included in these trials totaled at 1096 across 355 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.

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Head of VHIO's Clinical Research Oncology Nurses, Ángeles Peñuelas, pictured here with Supervisory Assistant Juan Manuel García. Our expert nurses are specialized in molecular therapies and are essential members of VHIO's multidisciplinary oncology teams.

Research at the UITM is led by Jordi Rodón'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 treatment regimens using combinations of new drugs with existing ones. In 2016, 115 Phase I clinical trials and 14 basket studies were performed at our Unit with a total of 453 patients enrolled. Our Clinical Trials Office, directed by Gemma Sala, coordinates a large portfolio of Phase I – II – III studies and consistently reports an increase in the number of trials conducted each year. In 2016 the number of patients included in our studies totaled at 1129 across 354 actively recruiting trials.

VHIO's direct access to cancer patients: crucial to our purely translational research model

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 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. Research at VHIO therefore benefits immensely from its privileged location; just a few meters away from the Campus, and the superb interaction and teamwork with clinical colleagues at HUVH.

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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.

Commandeering research aimed at combating cancer

2017 celebrated a record breaking year in both the number and impact of scientific papers published. 282 scientific articles were published by VHIO researchers as corresponding/senior or co-authors with a cumulative Impact Factor (IF) totalling at 2851.

These figures reflect an increase in scientific productivity as well as the importance of VHIO's research contribution to the oncology field. For the complete list of articles published by VHIO researchers and clinical investigators in 2017 click here. To view this year's selection of just some of the most relevant articles by VHIO faculty published in 2017, click here.

Hailing the arrival of new VHIO talents

In pursuit of new emerging research areas at VHIO we were fortunate to welcome the following new talents to our Institute throughout 2017: Throughout this year, Sandra Peiró, PI of our Chromatin Dynamics in Cancer Group, has been busy consolidating her lab. Her group elucidates the epigenetic mechanisms controlling the expression of genes during tumor progression, with special emphasis on the role of the primary structure of chromatin fiber, as determined by histone tail modification, and the 3D chromatin structure implicated in transcription regulation. By identifying the molecular mechanisms of chromatin conformation changes in tumor cells they strive to unveil potentially druggable proteins.

As Junior Principal Investigator of VHIO's Applied Genetics of Metastatic Cancer Group, Leticia de Mattos-Arruda's research centers on integrating multi-omics data towards better understanding of tumor heterogeneity and the role of the immune system within and between tumors. She also focuses on identifying novel biomarkers to guide the selection of anti-cancer therapies based on the specificities of individual patients and advance insights into differential clinical responses in individuals with metastatic breast cancer.

Towards the end of the year a further two Principal Investigators joined VHIO: Raquel Perez-Lopez moved to VHIO in October from the Institute of Cancer Research - Royal Marsden Hospital, where she conducted her PhD under the supervision of Johann de Bono, to head up our newly established Radiomics Group.

As Principal Investigator, Raquel's research will center on functional CT and MRI techniques such as perfusion, diffusion and spectroscopy, to better identify the histological and molecular characteristics of tumors. Her group will seek to optimize drug development by more effectively characterizing the antitumor effect of novel agents including immunotherapies, identify those patients who are most likely to benefit from these therapies, and further enforce our translational research programs in genomics, predictive science, and biomarkers of response and resistance.

Raquel has already established interdisciplinary collaborations with various VHIO groups, and soon she will welcome an MR researcher for novel imaging biomarker development and an MSc student and clinical research fellow on her team. Also joining us from the same institution (and mentorship) is Joaquin Mateo, as Principal Investigator of our recently created Prostate Cancer Translational Research Group.

Leading research aimed at translating prostate cancer genotypes into phenotypes and a clinically-relevant classification of the disease, he will also build a precision medicine core for prostate cancer patients. Joaquin has already recruited three group members to join us early in 2018, and, together with our Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group, led by Joan Carles, has launched a program to prospectively acquire samples from metastatic lesions and circulating biomarkers from patients with metastatic prostate cancer treated at the Vall d'Hebron University Hospital (HUVH).

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From left to right:
Sandra Peiró, Principal Investigator, Chromatin Dynamics in Cancer.
Leticia de Mattos-Arruda, Junior Principal Investigator, Applied Genetics of Metastatic Cancer.
Raquel Perez-Lopez, Principal Investigator, Radiomics.
Joaquin Mateo, Principal Investigator, Prostate Cancer Translational Research.

Liquid biopsy and the less invasive tracking of cancer

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

As a direct reflection of our expertise in developing this approach at clinical level, driven in collaboration with our Cancer Genomics Group, VHIO counted two out of the five projects selected under the TRANSCAN Joint Translational Call on Minimally and non-invasive methods for early detection and/or progression of cancer.

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Awarded by the Spanish Association against Cancer (AECC) and the Institute of Health Carlos III (ISCIII) through the ERA-NET TRANSCAN-2 program funded by EU's Horizon 2020, the first of VHIO's two TRANSCANs, led by Enriqueta Felip, Principal Investigator of our Thoracic Tumors & Head and Neck Cancer Group, will establish non-invasive prognostic markers for resected early stage non-small lung cancer (NSCLC) by assessing the role of circulating and exosomal miRNAs and free circulating DNA (fcDNA).

The second, directed by Elena Élez, Medical Oncologist and Clinical Investigator of VHIO's Gastrointestinal & Endocrine Tumors Group, focuses on the early detection of relapse in advanced colon cancer patients by longitudinally following a personalized molecular signature by liquid biopsy. This proof-of-concept, prospective and multi-center study seeks to evaluate the clinical feasibility of tracking tumor progression by dynamically detecting a molecular signature from a blood test.

To essentially pave the way for projects to come, we are currently setting up our in-house plasma bank, Seroteca, to centralise the collection and management of blood samples from all patients participating in research projects at VHIO. This excellent resource will significantly advance the clinical validation of liquid biopsy across tumor types.

The power of collaboration of excellence: at home and away

Task-forcing team science

VHIO's expert and interdisciplinary taskforces, coordinated by Alejandro Piris, our Scientific Research 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, among others.

Currently counting seven groups covering colorectal, breast, lung, gynecologic, prostate, melanoma tumor types as well as immunotherapy, our taskforces regularly convene to synergize efforts, boost collaborations among groups and between specialists, and continuously revise respective circuits and ethics toward advancing cancer science and medicine.

In line with recommendations outlined in our Scientific Advisory Board's 2017 Report, and to complement and expand our priority research areas, we will seek to further develop and functionalize our appointed taskforces as well as strengthen our shared and standard operating procedures.

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Meetings of collaborative minds: VHIO's Colorectal Taskforce in action.

Strategic alliances between public entities across Catalonia

The Oncology Network of Catalonia is a strategic collaboration between two public entities: the Catalan Institute of Health (ICS) and the Catalan Institute of Oncology (ICO).

Scientifically led by Josep Tabernero in his capacity as Head of the Medical Oncology Department of the Vall d'Hebron University Hospital (HUVH), this network combines the expertise and critical mass toward further advancing precision oncology in the treatment and cancer of cancer patients.

This collaboration also represents a hub of research of excellence from within the region and connects renowned institutes that are dedicated to further spurring innovation, cancer discovery and therapeutic advancements.

Its clinical research program incorporates therapies in currently conducted trials and aims to spur competition in the design and initiation of new studies as well as improved molecular diagnostics.

Updating on VHIO's participation in international consortia of excellence

VHIO believes in combining strengths and overcoming current challenges in oncology in concert, and consequently (co) identifies, develops and cements important partnerships globally. Important updates concerning our participation in existing collaborations are as follows:


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Cancer Core Europe (CCE) is a unique partnership aimed at addressing the cancer care cancer research continuum. Launched in the Autumn of 2014, this working consortium represents a critical mass of activity for the successful integration of all cancer care information, clinical research and outcome research.

CCE is led by its six 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), and VHIO.

Recently incorporating The National Cancer Institute of Milan (Italy), CCE promotes the pooling and exchanging of latest research findings, the sharing of platforms and processes, and empowers researchers and clinicians to rapidly exploit this trove of biological insights and clinical data for the benefit of patients.

VHIO has led the design of the Cancer Core Europe's endorsed Basket of Baskets (BoB) trial. This academic study will integrate molecular prescreening, the development of new diagnostic tests such as circulating DNA, with the testing of targeted therapies in populations of patients who, matched to the molecular alterations detected in their respective tumors, will be most likely to benefit from them.

In 2017 the protocol of its first module supported by a pharmaceutical company, Immune-Checkpoint Blockade in Genomically Selected Populations, was approved. Protocol title: A Modular, Open-label, Phase II, Multicentre Study to Evaluate Targeted Agents in Molecularly Selected Populations With Advanced Solid Tumours.

The protocol will be sent to the relevant authorities next year and first patient enrolment is envisaged towards the end of 2018.
www.cancercoreeurope.eu


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As a reflection of our expertise in developing and finely tuning cancer models to identify factors influencing tumor growth, predict cancer progression and response to treatments, VHIO is both founding member and member of the Board of Coordinators for strategic decisions and management of the EuroPDX Consortium – Translating Knowledge in Oncology. Established in 2013, it connects 20 institutions across 9 EU countries and the US that are developing PDX cancer models, promotes the sharing and exchange of findings on promising therapeutics, and leads multicenter preclinical studies.

As highlighted in our Director's Foreword this year, EurOPDX members co-authored an important article* exploring the current challenges of patient-derived xenografts (PDX). The review assessed the progress marked to-date in developing these and other models to more faithfully recapitulate the molecular specificities of patient samples, and balanced preclinical realities with current expectations from the clinical perspective.

Following their review of using next-generation models to establish the role of the immune system in tumor cell spread and test-bed the increasing portfolio of immunotherapeutics, co-authors also stressed the absolute necessity of sharing and exchanging data from various experimental models– a guiding principle that defines both the EurOPDX Consortium and VHIO.
www.europdx.eu

*Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinská E, Caldas C, Chang DK, Clarke RB, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek MA, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer HG, Peeper DS, Pelicci PG, Piris-Gimenez A, Roman-Roman S, Rueda OM, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Apr;17(4):254-268.


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Spurred by Horizon 2020's European Union funding for Research and Innovation funding, MoTriColor (Molecularly guided Trials with specific treatment strategies in patients with advanced newly molecular defined subtypes of Colorectal cancer), led by VHIO, is powered by a total of eight clinical research centers of excellence, spanning Spain, Italy, The Netherlands and Belgium, as well as the European Organisation for Research and Treatment of Cancer (EORTC), and a diagnostic/prognostic SME.

Dedicated to conducting multi-center early phase clinical trials to establish the anti-tumor activity of novel experimental therapies for patients with metastatic or advanced colorectal cancer, patients will be stratified based on their gene expression profiles according to recently established predictive signatures, and response and resistance to selected therapies will be tracked by liquid biopsy.

This year, prescreening is currently underway and patient enrolment in the three clinical trials commences in 2018.
www.motricolor.eu


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Initiated in 2010, WIN's Worldwide Innovative Networking (WIN) Consortium in personalized cancer medicine aims at rapidly translating precision cancer medicine discoveries into standards of patient care worldwide. Currently comprising 43 partners including VHIO, this global collaboration strives to up the tempo and reduce the costs of translating novel cancer treatments to the clinic by developing and applying the most promising genomic-based research advances.

Building on the unique, academic and international trial, WINTHER (WIN Therapeutics) selected partners have designed a second WIN trial: Survival Prolongation by Rationale Innovative Genomics (SPRING). Bringing key stakeholders together from industry and academia, this collaboration will focus on advancing precision medicine against lung cancer.

In 2017 the Consortium received the US Food and Drug Administration's (FDA) approval to start the clinical investigation of a novel therapeutic approach using the combination of three targeted therapies for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC).
www.winconsortium.org


Other partnering opportunities in 2017

VHIO and the Memorial Sloan Kettering Cancer Center - MSKCC (New York) recently renewed its collaborative framework agreements as follows:

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The Obra Social ”la Caixa” 2nd International Program for Cancer Research and Education, renewed as a 3-year initiative to consolidate and further pursue the established synergies between VHIO and MSKCC.

This new project will include several initiatives focused on the pan-omic exploration (genomics and radiomics) of solid tumors, with particular emphasis on Big Data. More specifically, with José Baselga, Physician-in-Chief at MSKCC and myself as co-PIs (in collaboration with Maurizio Scaltriti, MSKCC, and VHIO's Rodrigo Dienstmann, Ana Vivancos, Joaquin Mateo and Raquel Perez-Lopez), we will conduct research on the impact of gene mutations in DNA damage repair and metastatic prostate cancer, together with data mining to reveal new molecular genetic determinants of sensitivity to targeted therapy in solid cancers.


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VHIO and the BBVA Foundation paired in collaboration with MSKCC to pioneer a Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI). Building on the successes of a previous joint project to implement a tumor biomarkers research program, 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.

This project combines the expertise of VHIO's Elena Garralda (PI of VHIO's Early Clinical Drug Development and Executive Director of our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”), who heads up CAIMI's clinical research, Alena Gros (PI, VHIO's Tumor Immunology and Immunotherapy Group), who takes the lead on translational research, and Ana Vivancos (PI of our Cancer Genomics Group), who directs our internationally recognized prescreening platform. In collaboration with our MSKCC colleagues, VHIO will co-found six translational projects linked to the early clinical development phases of immunotherapy.


Institutional accolades & accreditation

“HI-5'd” by the European Alliance for Personalised Medicine for best integrating personalized medicine in oncology

This year's European Alliance for Personalised Medicine (EAPM) Congress: Personalising Your Health: A Global Imperative, 27 – 30 November (Belfast, Ireland), celebrated the launch of its Health Innovation Five ‘HI-5’ Awards. In recognition of VHIO's purely integrative and comprehensive research model that tightly connects cancer discovery with clinical research, our Institute was awarded under the category of Best EU-based hospital for integrating personalised cancer medicine.

This coveted prize salutes VHIO's capacity to swiftly integrate and transform precision medicine against cancer.

2017 Best-in-Class Prize awarded by Gaceta Médica

Also announced in 2017, VHIO was awarded with Gaceta Médica's Best-in-Class Prize for R&D in oncology in recognition of our contribution to the Spanish National Health System.

This accolade recognizes VHIO as a leading comprehensive cancer center of excellence and our capacity for turning cancer discovery into more powerfully tailored treatments and better practice for the care of patients.

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From left to right: Sergi Cuadrado, VHIO's Deputy Managing Director, Josep Tabernero, Director of VHIO, Joan Seoane, Director of Translational Research, Joan Carles, PI, Genitourinary, CNS Tumors & Sarcoma Group, pick up Gaceta Médica's 2017 Best-in-Class Prize.

Recognition through accreditation

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In 2017 VHIO underwent evaluation for accreditation of the CERCA Institute of Research Centres of Catalonia (Institució CERCA – Centres de Recerca de Catalunya) for the period 2013 – 2016. In recognition of VHIO's progress, performance in knowledge transfer activities and management of excellence, VHIO was awarded with the maximum qualification of an A grading.

Also reflecting our dedication to excellence and the quality of our services and procedures, our Cancer Genomics and Molecular Groups, led by Ana Vivancos and Paolo Nuciforo respectively, have both received ISO 15189 accreditation for their testing methods and technologies. Similarly, we continue to meet the high standards in quality and procedures in the audit of our clinical trials Units, carried out by the Generalitat de Catalunya. Our Research Management is also endorsed by ISO 9001 Certification.

Translational insights spurring VHIO Spin-Offs

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Establishing the role of leukemia inhibitor factor (LIF) as a promoter of cancer progression and the discovery of humanized antibody MSC-1's capacity to effectively target LIF, VHIO's translational research led to the launch of VHIO-born spin-off Mosaic Biomedicals S.L. , and the promise of the accelerated clinical development of MSC-1.

Mosaic Biomedicals, co-founded in 2014 by VHIO's Joan Seoane (Director of our Translational Research Program and ICREA Professor), merged with a Canadian company, Northern Biologics in 2016, and will run a clinical trial across sites at VHIO, Memorial Sloan Kettering Cancer Center (MSKCC) and the Princess Margaret Hospital in early 2018.

In 2017 Mosaic was co-recipient of CataloniaBio's Biosuccess Award of the Year for its exceptional entrepreneurship and biobusiness development aimed at advancing healthcare. This year's prize also recognized the aforementioned merger consequent promise of the humanized antibody MSC-1.


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Built on research carried out at VHIO to successfully translate Omomyc-based therapy into clinical application, a second VHIO spin-off, Peptomyc S.L., co-founded by VHIO's Laura Soucek in 2014 (PI of our Mouse Models of Cancer Therapies Group, ICREA Professor, and CEO of Peptomyc) centers on developing anti-Myc peptides for the treatment of non-small cell lung cancer, triple negative breast cancer and glioblastoma. The Omomyc cell-penetrating peptide (CPP), proven preclinically, promises to become the first ever clinically viable and direct inhibitor of Myc – a protein implicated in the formation of most tumor types.

In 2017 this spin-off secured 4.2 million euros in a Series A round led by the Barcelona-based venture capital investment firm, Alta Life Sciences. This funding will provide Peptomyc with the necessary capital for the development of clinical trials to test this novel peptide for the inhibition of MYC.


VHIO-organized events: exchange and debate of latest discovery to spur progress against cancer

VHIO is highly dedicated to organizing events of the highest calibre to provide unparalleled opportunity to present, debate and discuss the very latest in cancer discovery – from the bench to bedside and back. These educational opportunities frequently lead to new and essential research collaborations that continue to accelerate our collective efforts aimed at solving cancer sooner.

VHIO-organized events: exchange and debate of latest discovery to spur progress against cancer

Launched back in 2011 VHIO's Meet the Editors series are special sessions providing oncology professionals at research institutes of excellence in Barcelona with unique opportunity to learn more about scientific publishing and 'hot spot' areas of cancer research, as well as put questions and comments directly to editors during the Q&A with the audience.

Over the last few years we have been fortunate to have welcomed Senior Editors of some of the most prestigious publications in oncology and biomedicine including Nature, Nature Reviews Cancer, Science, The New England Journal of Medicine, Nature Medicine, Cancer Cell, The Lancet Oncology, Cancer Discovery and Annals of Oncology.

As this year's Report goes to print, Barbara Marte, Senior Editor, Nature, will return to VHIO for a day with several of our Principal Investigators. We also envisage a VHIO Meet the Editors session this year with Kevin Davies, Founding Editor, Nature Genetics, former Editor-in-Chief of Cell Press, and Executive Editor of the newly launched, The CRISPR Journal.

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 30 Courses, Workshops, Observerships and Perceptorships in 2017.

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1.- Preceptorship in the Management of Advanced Prostate Cancer: Multidisciplinary Approach, 16- 17 March 2017, Coordinator: Joan Carles 2.- Breast Cancer Preceptorship Programme, 13 – 15 September 2017, Coordinator: Cristina Saura 3.- Colorectal and Gynecological Malignancies (RIME), Dates: 15 – 17 November 2017, Coordinator: Elena Élez.


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Launched in February 2016 by co-Chairs Verónica Rodilla and Jordi Martínez Quintanilla, Post-Doctoral Fellows of VHIO's Growth Factors and Stem Cells & Cancer Groups respectively, 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.

In 2017, a total of 17 researchers presented, discussed and 'benchstormed' their research areas.

The welcoming and hosting of other meetings

Our move to VHIO's new premises, the CELLEX Building, back in 2015 has not only provided us with the valuable space through which to our research programs, but also gave us a state-of-the-art auditorium. It is with huge thanks to the CELLEX Foundation that we can now happily and readily review requests received from our project partners as well as leading societies in oncology to host and celebrate their respective scientific meetings and conferences.

As an example, in 2017 we welcomed the EU FP7-supported REQUITE project's 5th annual gathering and 9th anniversary of the Radiogenomics Consortium meeting, 19 – 21 June. This hosting was spurred by VHIO's Orland Díez's and Sara Gutiérrez's (Principal Investigator and Senior Scientist of our Oncogenetics Group, respectively), participation in REQUITE – Validating predictive models of radiotherapy toxicity to improve quality-of-life and reduce side-effects in cancer survivors.

Throughout the course of the meeting participants updated on important progress reported from various cross-border studies that are developing and validating statistical models incorporating biomarker to establish the likelihood of adverse side-effects, explored the application of machine learning techniques to radiogenomics, and road-mapped next directions in a session dedicated to future projects.

REQUITE's two-day annual meeting showcased latest developments across its various work packages with up-to-the-minute results from its various studies and trials.


Coming to VHIO in 2018

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An EACR masterclass: LIF as We Know It: From Basic Science to Clinical Trials.

Organized by Joan Seoane, Director of Translational Research at VHIO and ICREA Professor, in collaboration with the European Association for Cancer Research (EACR), LIF as We Know It: From Basic Science to Clinical Trials, will be coming to VHIO's CELLEX Auditorium, Barcelona, 28 – 29 May 2018, for a bench-bedside and back review of all the very latest insights in the field of LIF.
www.eacr.org/conference/lif2018.


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.

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In 2017 we celebrated the launch of two new public engagement activities: VHIO's Running for Research and our Schools and Science Education Program:

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Inspired by Daniel Massó Vallés and Irene Rius, Post-Doctoral Fellow and Graduate Student of VHIO's Mouse Models of Cancer Therapies and Growth Factors Groups, respectively, VHIO's Running for Research currently comprises a team of 15 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.

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VHIO runners with our Director, Josep Tabernero.

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

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VHIO's new education program, Schools and Science, welcomed over 50 under-twelves from a local primary school to meet our faculty, tour our laboratories and learn more about cancer biology and research.

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VHIO's Violeta Serra, PI of our Experimental Therapeutics Group delivering a junior masterclass at CELLEX on the origins and development of cancer.

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 visit our young visitors participated in workshops and hands-on activities 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 inspired program, with dates already in the diary for next 2018.

Continued evolution: VHIO's international and internal scientific communication

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www.vhio.net: the face of VHIO and the main way in which we communicate with the international oncology and scientific community.

VHIO's web portal and content is principally aimed at the multidisciplinary, international oncology community and exists to report on all the latest research, developments and activities of our expanding faculty as well as important outcomes from VHIO's broad range of projects.

VHIO's International Communications, directed by Amanda Wren, is focuses on upgrading and constantly updating our website's content, adding new programs as they launch, and implementing new features aimed at further generating traffic, maintaining and attracting new visitors.

At the end of 2017 we launched our new, fresher look website as we transitioned from our previous content management platform:

Our new portal has afforded us more flexibility with exciting opportunities to create interactive content, upload videos, rotating banners, dynamic illustrations and figures to complement the written word.

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Launched in December 2017, 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 Communication Director's surname, incorporates a silhouette of the Wren species perched on top of a lens accentuating VHIO's logo (not to be mistaken for Twitter's bird!).

Initially intended as an internal publication, upon tracking the ‘flight’ of this e-publication, we are seeing that external shares are on the up.

A Golden Decade: reflecting on the past 10 years of VHIO's translational success story

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10 years' translational cancer research: the barometer of VHIO's success

The Vall d'Hebron Institute of Oncology (VHIO) was officially established in 2006 by our former Director, José Baselga, now Physician-in-Chief at the Memorial Sloan Kettering Cancer Center (MSKCC, New York), President of VHIO's Internal Scientific Committee, and Founder and President of the FERO Foundation.

From the outset, José had one pioneering and guiding principle for VHIO: to seamlessly bridge preclinical and clinical research in order to foster a continuous virtuous cycle of knowledge from bench to bedside and back. As evidenced throughout this Scientific Report, this bold approach continues to be at the very core of VHIO's philosophy, passionately pursued by our strong multidisciplinary teams.

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Back in 1990: José Baselga in John Mendelsohn's Laboratory, MSKCC, where he pioneered trastuzumab (Herceptin) against HER2 positive breast cancer.

As early as 1990, José was carving out a new paradigm for cancer research through the translational approach – a concept which has only relatively recently been embraced by the professional cancer community. During his time at the prestigious Memorial Sloan Kettering Cancer Center (MSKCC) and Memorial Hospital in New York, he developed and conducted clinical and translational research in parallel – many years before the term ‘translational’ entered the oncology lexicon.

Specifically, he was responsible for conducting preclinical studies and leading a clinical trial to test the potential therapeutic effects of trastuzumab, a monoclonal antibody anti-HER2.The molecule proved highly efficacious in treating breast cancer patients that overexpressed this receptor and for whom life expectancy was very low at that stage. Numerous patients' lives have since been saved after being treated with this molecule and HER2 positive breast cancer is thankfully no longer as frightening a disease as it used to be.

Returning to the Vall d'Hebron University Hospital (HUVH) in 1996 to lead its then very small Medical Oncology Department, José's vision, work ethic and impeccable commitment to medical oncology quickly lifted the department to new heights. These qualities coupled with his devotion to integrating translational science and clinical research, rapidly established the department as an international reference. José created an environment in which optimal patient care is conciliated with innovative translational research, all in the context of a Public Health System – an exemplary model that has since been adopted and adapted across borders.

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Josep Tabernero, Director of VHIO and our Clinical Research Program, with José Baselga and VHIO's two other Program Directors, Joan Seoane – Translational Research (far left), and Joaquín Arribas – Preclinical Research (far right), back in 2013.

This not only extended his translational approach to multidisciplinary teams but also emboldened him to create VHIO, which has over the past decade become a leading comprehensive cancer center of international acclaim. José turned his unique vision into a reality: aided by direct access to patients and his purely translational model VHIO has rapidly gained its rightful place as one of the few cancer institutes to swiftly transform discovery in oncology into benefits for patients.

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In 2017: the European Society for Medical Oncology (ESMO) honoured José Baselga with the ESMO Lifetime Achievement Award for his crucial role in breast cancer drug development. His pivotal laboratory and clinical studies have led the approval of trastuzumab, pertuzumab and everolimus, among many other groundbreaking therapies across other tumor types including cetuximab. Photo courtesy of ESMO.

His strategy has been widely adopted as the model of excellence in the current era of precision oncology against this brutal disease that continues to outsmart and evade our most powerful arsenal of anti-cancer weaponry. In short, José's vision establishes him as one of the godfathers of this connective, multidisciplinary approach.

“Oncology, like no other field, is defined by its collaborative nature and I have been blessed by having worked over the years with wonderful trainees and clinical and laboratory scientists. This award goes to them." José Baselga, Physician-in-Chief, Memorial Sloan Kettering Cancer Center - MSKCC (New York).

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Josep Tabernero, VHIO's Director and current President of the European Society for Medical Oncology (ESMO).

Year in, year out, our talented teams continue to report important developments in exposing the many previously hidden cancer drivers, harness vast amounts of data, step up the pace in turning discovery into real benefits for an increasing number of patients, and innovate our research approaches and clinical trial design based on precious insights provided through this translational research.

I would like to close this introduction to A Golden Decade by saluting José Baselga, without whom none of VHIO's many achievements and important contributions to solving cancer sooner would have been possible.

Lastly but by no means least, I thank our amazing institutional supporters, our private patrons: the FERO Foundation (FERO Fundación de Investigación Oncológica), CELLEX Foundation (Fundació Privada CELLEX), ”la Caixa” Foundation (Fundació Bancària ”la Caixa”), BBVA Foundation (Fundación BBVA), and the support received from our public patron, the Government of Catalonia (Generalitat de Catalunya).

I would also like to express my gratitude to our many other supporters and partners for their continued and devoted belief and backing of our research.

Only with this precious funding can we continue to do what we do best: translate our discoveries in oncology into more precise, individualized treatment and care of patients suffering from cancer.

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

Raising the roof in VHIO's ambitions to solve cancer sooner

With VHIO's translational and multidisciplinary model came a strategically devised expansion plan and with it, major reconstruction and the introduction of new facilities, research units and ultimately, an entire new building – quite literally raising the roof in VHIO's ambitions to solve cancer sooner:

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New facilities and reform rounds to promote multidisciplinary breast cancer of excellence

Further to the completion of a first phase development in 2003, 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.

Spanning 988 m2, the then new premises was especially designed to connect and link both services along one corridor. Financed entirely by the CELLEX Foundation, 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, promotes the purely translational and multidisciplinary model for which VHIO is famed.

Not only has this essential and complete infrastructural makeover provided the necessary space that was so desperately needed for our patients and our multidisciplinary and transversal oncology teams alike, it has also led to increased efficiency and excellence in the services we provide.

From the initial planning...

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... to this in 2008:

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2008: marking a crucial year of new agreements and an inaugural celebration

The year 2008 laid the very first ‘paper’ foundations for two major new projects:

First, the agreement was written up and signed between VHIO and the CELLEX Foundation (Fundació Privada CELLEX) for the construction of a brand new, state of the art research building to centralize all VHIO's programs, teams and technologies in the same physical space and thus further promote the multidisciplinary and translational two-way interaction and exchange between VHIO's cancer researchers and physician-scientists en force .

Representing another groundbreaker in VHIO's translational 10 year history was the signing of the agreement for the construction of our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, driven by support received from the ”la Caixa” Foundation (Fundació Bancària ”la Caixa”). This Unit was established to lead early phase clinical trials with novel drugs and therapeutic targets to potentiate the efficacy of anti-cancer therapies and reduce toxicity (click here).

2008: the inauguration of our internationally renowned Breast Cancer Center

Located on two floors of our Hospital's Maternity and Pediatrics Building, our Breast Cancer Center “Endavant i de Cara” (loosely translated as ‘upwards, head high’), was financed through a personal donation received from Maria Angels Sanahuja, an ex-patient of José Baselga, in memorium of Roman Sanahuja and Francisca Pons.

Dedicated to advancing the prevention, treatment and care of breast cancer patients by pooling and combining expertise across all specialties in multidisciplinary teams, our Center houses the entire circuit of patient care incorporating all the necessary services and spaces including consultancy rooms, screening facilities and technologies, radiomics, latest diagnostics, and pharmacy.

Inaugurated by Her Majesty the Queen Sofía of Spain, 30 April 2008, the Center was initially directed by José Baselga under the co-leadership of Deputy Director, and former Principal Investigator of VHIO's Breast Cancer and Melanoma Group, Javier Cortés (see 2008 group picture in the photo collage below). This trailblazing tandem quickly established the our Center and its clinical research group as a leading reference in advancing personalized treatment and care against breast cancer.

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An inaugural celebration of VHIO's Breast Cancer Center back in 2008.

Our translational and multidisciplinary breast cancer program, spearhead by VHIO's Cristina Saura since 2015, continues to be one of the most active and recognized throughout Europe by significantly advancing novel and more precise anti-cancer therapies to improve outcomes for patients suffering from this disease (click here).

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2010: VHIO's Research Unit for Molecular Therapies of Cancer (UITM) – ”la Caixa” opened its doors to pioneer early drug discovery and clinical studies tailored to the specificities of patients

Knowledge of the molecular biology of cancer has grown exponentially over the last decade and this in turn has meant the identification of a host of therapeutic leads for the development of selective drugs.

Directed by Josep Tabernero, Director of VHIO as well as our Clinical Research Program (click here), under the former coordination of Jordi Rodón, our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa” was inaugurated on 23 June 2010, thanks to the essential support received from the ”la Caixa” Foundation (Fundació Bancària ”la Caixa”), in order to develop novel therapies based on the molecular profile of each tumor and optimize treatment strategies using combinations of new agents with already existing ones:

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Research at the 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.

Now coordinated by Elena Garralda as UITM's Executive Director, our Unit goes from strength to strength each and every year. It continues to grow its portfolio of studies and fine-tune patient selection criteria and stratification based on intrinsic biological intelligence and a more precise classification of cancers. In 2017, 120 Phase I clinical trials and 17 basket studies were performed at our Unit with a total of 445 patients enrolled.

From this in 2008…

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…to this in 2010:

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2015: The CELLEX Building

As previously mentioned, the initial agreement paving the way for VHIO's new home was signed by VHIO and the CELLEX Foundation (Fundació Privada CELLEX) was formalized in 2008. Under Josep Tabernero's leadership, the construction of the CELLEX building commenced in 2012 and was completed in 2015. Marking a new VHIO chapter, our new premises provided the necessary space and amenities to expand our research activities and further foster the already existing multidisciplinary connectivity and exchange by bringing all VHIO's research teams together under the same roof.

Key to advancing predictive cancer models, and representing the final jewel in the crown of the construction of the CELLEX Building, VHIO's cutting edge Animal Facility opened for business in 2016. Occupying the basement of our building, it serves as a shared facility across the Vall d'Hebron Barcelona Hospital Campus, spans a surface area of 1347 m2, and is equipped with 5500 cages.

Incorporating the latest platforms and technologies for analyzing small animal models of human disease, VHIO's expertise in developing and rendering cancer models including patient derived xenografts (PDX) more precise and predictive, has further expanded thanks to this cutting-edge facility.

Providing the valuable space through which to grow, the CELLEX Building has not only further enhanced collaborations and accelerated our dedicated efforts to combat cancer, it has also allowed us to more hotly pursue new emerging research areas including immunology & immunotherapies, as well as fortify our research structure. In fact, since we occupied our new premises, VHIO's full-time equivalents (FTEs) in research now totals at 254.37.

From this in 2012…

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Potentiating VHIO's programs, groups and technologies

In addition to new buildings and facilities, VHIO's successes marked to-date have only been possible thanks to the tremendous support received from our other two private patrons, the FERO Foundation (FERO Fundación de Investigación Oncológica), and the BBVA Foundation (Fundación BBVA), as well as the funding it receives from our public patron, the Government of Catalonia (Generalitat de Catalonia), international and national competitive grants, private institutions, companies, and individuals (click here for the full listing in 2017).

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Our cherished public patron, the Government of Catalonia: dedicated supporter of cancer science and medicine of excellence

From the very outset, the Government of Catalonia (Generalitat de Catalonia) and more specifically, the Catalan Departments of Finance and Health, has been a keen and devoted ambassador of VHIO and our various research programs and projects. As one of our Founding Patrons, it has been institutionally and financially supporting us throughout our Golden Decade and now, beyond, with the Catalan Minister of Health as the President of our Board of Trustees.

VHIO's translational and multidisciplinary approach to cancer research is only possible through the connectivity and tremendous collaboration we have with the entire spectrum of oncology professionals at our hospital, the Vall d’Hebron University Hospital – HUVH, and the rest of the Catalan Public Health System.

Worthy of special mention, as we reflect on the first ten years of VHIO’s relatively short existence, is the pivotal role played by the Catalan Department of Health in integrating VHIO’s research activity into the Catalan Health System, representing a remarkable example of how the public and private sectors can successfully collaborate 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 essential collaboration affords us access to the Catalan Research System and the fiscal and legal benefits that this represents.

Last but not least, the financial support provided by the Government of Catalonia has contributed majorly to VHIO’s structural overheads, allowing us to center our efforts on our core research activities.

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FERO Foundation: faithful promoter of new VHIO talents

The precious support received through FERO over the last decade has enabled science of excellence at VHIO as well as promoted and grown the careers of up-and-coming talents in oncology. Concerning the former, to name but two, the labs of both Josep Villanueva, PI of our Tumor Biomarkers Group, and Laura Soucek, PI of VHIO's Mouse Models of Cancer Therapies Group and ICREA Professor, have significantly been able to grow their groups and advance their pioneering research lines thanks to FERO.

More specifically, Josep, who joined VHIO in 2009 to advance biomarker and drug target discovery toward ultimately enabling a more precise diagnosis and monitoring of cancer therapies, received funding, thanks to FERO, through a donation from the Josep Botet Foundation (Fundació Josep Botet), to finance the implementation in 2010 of the LTQ-Orbitrap Velos mass spectrometer.

In 2011 we attracted another new talent, Laura Soucek, who joined us thanks to a FERO start-up grant twinned later that year with a highly coveted FERO Award. This funding, along with support received from other entities, has not only contributed to the growth of her team from two investigators to a total of eleven (2017), but also helped them to pursue and advance research aimed at preclinically validating novel anti-Myc therapies across various tumor types.

Regarding FERO's Annual Award for Translational Research, as a further reflection of VHIO's sustained cancer discovery of excellence, a total of six of our research scientists have been honored with this prize:

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Laura Soucek (2011), Héctor G. Palmer (2012), Ibrahim Yasir (2013), César Serrano (2015), Beatriz Morancho (2016), and María Abad (2017).

Importantly as an example this year, funding received from FERO has also financed our recently incorporated Droplet Digital PCR (ddpCR) Bio-Rad Technology platform, and we are already making significant progress in validating and developing this technology for the more effective and less invasive tracking of cancer by liquid biopsy.

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

Combining expertise of VHIO with colleagues at Massachusetts General Hospital Cancer Center – MGHCC (Boston), where José Baselga was at the time Chief of Hematology and Oncology, the BBVA Foundation launched the Tumor Biomarkers Research Program back in 2011.

Under the co-scientific direction of José Baselga and Josep Tabernero, this five-year major framework agreement fueled collaborative science centering on the development of personalized therapies for cancer patients through biomarker research.

As a direct reflection of the importance of this program, only made possible through the essential funding we received from the Foundation, 26 scientific articles generated through this research were published in top-tier journals of excellence. Important findings were also reported as 8 posters during several must-attend international congresses within our field.

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(Left) The signing of our 2011 BBVA Foundation framework agreement. (Right) The 2017 launch of our BBVA Foundation framework agreement: the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI).

VHIO and the BBVA Foundation this year renewed their agreement in collaboration the Memorial Sloan Kettering Cancer Center - MSKCC (New York). Building on the successes 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 superb co-leadership of José Baselga in his current capacity as Physician-in-Chief at MSKCC, and Josep Tabernero, Director of VHIO, this ambitious project counts on the expertise of VHIO's Elena Garralda (PI of VHIO's Early Clinical Drug Development and Executive Director of our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”), who heads up CAIMI's clinical research, Alena Gros (PI, VHIO's Tumor Immunology and Immunotherapy Group), who takes the lead on translational research, and Ana Vivancos (PI of our Cancer Genomics) who directs our internationally recognized prescreening platform.

In collaboration with our distinguished MSKCC colleagues, VHIO will co-found six translational projects linked to the early clinical development phases of immunotherapy.

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The launch of our 2017 BBVA Foundation framework program.

Our Golden Decade: a few more must-mentions

It is thanks to all the aforementioned support received from our treasured institutional supporters, and the critical funding from many other entities (click here for all a full listing in 2017), that we have been able to expand our programs and research lines.

We have also consequently been fortunate enough to grow our teams and personnel based on carefully planned strategic direction. The incorporation of all our new talents at VHIO over the years has enabled us to significantly advance translational science and medicine in oncology on the global stage as well as continue to render cancer treatment and care more precise.

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VHIO'S FTEs EVOLUTION (2010-2017)
*VHIO incorporates an additional 61,2 associated MD's FTEs (Oncology & Hematology) contracted by our Hospital

In science and medicine, according to a 2015 UNESCO report, as highlighted in a recent article (Clark J et al. Lancet. 2017), women undergraduates outnumber men and yet 72% of the global scientific workforce is male. We at VHIO are pleased to report that 74% of our current entire workforce is female.

While this statistic is certainly something to be celebrated as we continue to uphold and support gender parity, we at VHIO place strict emphasis is placed on contracting the right individual, with the necessary skill set matched to the requirements of a particular position.

One of our guiding principles is to contract, promote and grow all our talents, totally irrespective of gender. As such, VHIO constantly seeks to strengthen its policies and practices that, in turn, undoubtedly contribute to spurring our research of excellence.

VHIO discovery aimed at dismantling cancer's armory

Commandeering research aimed at thwarting this disease, our preclinical, translational and clinical investigators continue to report important advances in cancer biology and therapeutic oncology. Since 2007, published papers have increased from 66 to a total of 282 for this year. Similarly, cumulative Impact Factor has progressively risen from 500 back in 2007 to 2851 in 2017:

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Cumulative Impact Factor per year (2007-2017).

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Number of articles published by VHIO researchers from 2007 – 2017.




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In this Report's special A Golden Decade chapter, it would have been fitting to have selected a top-10 of papers published throughout VHIO's relatively young history. An impossible task!

We have therefore restricted our pick to 25. These are merely representative examples of the myriad contributions made by VHIO to advancing cancer science and medicine:


Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. N Engl J Med. 2015 Aug 20;373(8):726-36.

The consensus molecular subtypes of colorectal cancer. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. Nat Med. 2015 Nov;21(11):1350-6.

Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Tabernero J, Lenz HJ, Siena S, Sobrero A, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Yoshino T, Goldberg RM, Sargent DJ, Wagner A, Laurent D, Teufel M, Jeffers M, Grothey A, Van Cutsem E. Lancet Oncol. 2015 Aug;16(8):937-48.

Clinical response to a lapatinib-based therapy for a Li-Fraumeni syndrome patient with a novel HER2V659E mutation. Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratù G, Parra JL, De Mattos-Arruda L, Grueso J, Hernández-Losa J, Arribas J, Prudkin L, Nuciforo P, Scaltriti M, Seoane J, Baselga J. Cancer Discov. 2013 Nov;3(11):1238-44.

Active CREB1 promotes a malignant TGFβ2 autocrine loop in glioblastoma. Rodón L, Gonzàlez-Juncà A, Inda Mdel M, Sala-Hojman A, Martínez-Sáez E, Seoane J. Cancer Discov. 2014 Oct;4(10):1230-41.

Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy. Parra-Palau JL, Morancho B, Peg V, Escorihuela M, Scaltriti M, Vicario R, Zacarias-Fluck M, Pedersen K, Pandiella A, Nuciforo P, Serra V, Cortés J, Baselga J, Perou CM, Prat A, Rubio IT, Arribas J. J Natl Cancer Inst. 2014 Sep 24;106(11).

Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC. J Clin Oncol. 2015 Oct 20;33(30):3401-8.

Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Roselló S, Tops BB, van der Post RS, Argilés G, Skartved NJ, Hansen UH, Hald R, Pedersen MW, Kragh M, Horak ID, Braun S, Van Cutsem E, Tolcher AW, Tabernero J. Cancer Discov. 2015 Jun;5(6):598-609.

Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. De Mattos-Arruda L, Mayor R, Ng CK, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Nat Commun. 2015 Nov 10;6:8839.

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, Folch G, Gonzàlez-Juncà A, Sodir NM, Massó-Vallés D, Beaulieu ME, Swigart LB, Mc Gee MM, Somma MP, Nasi S, Seoane J, Evan GI, Soucek L. Nat Commun. 2014 Aug 18;5:4632.

Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel JM, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer HG, Vivancos A. Ann Oncol. 2017 Oct 1;28(10):2451-2457.

Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Grasselli J, Elez E, Caratù G, Matito J, Santos C, Macarulla T, Vidal J, Garcia M, Viéitez JM, Paéz D, Falcó E, Lopez Lopez C, Aranda E, Jones F, Sikri V, Nuciforo P, Fasani R, Tabernero J, Montagut C, Azuara D, Dienstmann R, Salazar R, Vivancos A. Ann Oncol. 2017 Jun 1;28(6):1294-1301.

A predictive model of pathological response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Nuciforo P, Pascual T, Cortés J, Llombart-Cussac A, Fasani R, Paré L, Oliveira M, Galvan P, Martínez N, Bermejo B, Vidal M, Pernas S, López R, Muñoz M, Garau I, Manso L, Alarcón J, Martínez E, Rodrik-Outmezguine V, Brase JC, Villagrasa P, Prat A, Holgado E. Ann Oncol. 2017 Oct 12.

A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. Cancer Discov. 2017 Jan;7(1):102-113.

Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer. Baselga, J; Cortes, J; Kim, S-B; Im, S-A; Hegg, R; Im, Y-H; Roman, L; Pedrini, JL; Pienkowski, T; Knott, A; Clark, E; Benyunes, MC.; Ross, G; Swain, SM.; CLEOPATRA Study Group. 2012. N Engl J Med. 366: 109-119.

Beta-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Tenbaum, Stephan P.; Ordonez-Moran, Pa; Puig, I;Chicote, I; Arques, O;Landolfi, S; Fernandez, Y; Raul Herance, J; Gispert, J D.; Mendizabal, L; Aguilar, S; Ramon y Cajal, S; Schwartz, Jr., S; Vivancos, A; Espin, E; Rojas, S; Baselga, J; Tabernero, J;Munoz, A;Palmer, H G. 2012. Nat Med. 18: 892-900.

USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the activation of TGF-beta signaling in glioblastoma. Eichhorn, P J. A.; Rodon, L; Gonzalez-Junca, A; Dirac, A; Gili, M; Martinez-Saez, E; Aura, C; Barba, I; Peg, V; Prat, A;Cuartas, I; Jimenez, J; Garcia-Dorado, D; Sahuquillo, J; Bernards, R; Baselga, J; Seoane, J. 2012. Nat Med. 18: 429-492.

The landscape of somatic copy-number alteration across human cancers. Beroukhim, R; Mermel, CH.; Porter, D; Wei, G; Raychaudhuri, S; Donovan, J; Barretina, J; Boehm, JS.; Dobson, J; Urashima, M; Mc Henry, K T.; Pinchback, RM.; Ligon, AH.; Cho, YJ; Haery, L; Greulich, H; Reich, M; Winckler, W; Lawrence, M S.; Weir, B A.; Tanaka, K E.; Chiang, Derek Y.; B, Adam J.; Loo, A; Hoffman, C; Prensner, J; Liefeld, T; Gao, Q; Yecies, D; Signoretti, S; Maher, E; Kaye, F J.; Sasaki, H; Tepper, JE.; Fletcher, JA.; Tabernero, J; Baselga, J; Tsao, MS; Demichelis, F; Rubin, M A.; Janne, PA.; Daly, MJ.; Nucera, C; Levine, R L.; Ebert, BL.; Gabriel, S; Rustgi, A K.; Antonescu, C; Ladanyi, M; Letai, A; Garraway, LA.; Loda, M; Beer, D G.; True, L D.; Okamoto, A; Pomeroy, SL.; Singer, S; Golub, TR.; Lander, ES.; Getz, G; Sellers, WR.; Meyerson, M. 2010. Nature. 463: 899-905.

TGF-beta Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma. Anido, J; Saez-Borderias, A; Gonzalez-Junca, A; Rodon, L; Folch, Gerard; Carmona, MA.; Prieto-Sanchez, RM.; Barba, Ignasi; Martinez-Saez, E; Prudkin, L; Cuartas, I; Raventos, C; Martinez-Ricarte, F; Antonia Poca, M.; Garcia-Dorado, D; Lahn, M M.; Yingling, J M.; Rodon, J;Sahuquillo, J; Baselga, J; Seoane, J. 2010. Cancer Cell. 18: 655-668.

Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epidermal Growth Factor Receptor, in Patients With Advanced Solid Tumors. Paz-Ares, LG; Gomez-Roca C, Delord JP, Cervantes A, Markman B, Corral J, Soria JC, Bergé Y, Roda D, Russell-Yarde F, Hollingsworth S, Baselga J, Umana P, Manenti L, Tabernero J. J Clin Oncol. 2010; 29: 3783-3790.

CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S, Chheda MG, Tamayo P, Finn S, Shrestha Y, Boehm JS, Jain S, Bojarski E, Mermel C, Barretina J, Chan JA, Baselga J, Tabernero J, Root DE, Fuchs CS, Loda M, Shivdasani RA, Meyerson M, Hahn WC. Nature. 2008 Sep 25;455(7212):547-51.

Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. Tabernero J, Rojo F, Calvo E, Burris H, Judson I, Hazell K, Martinelli E, Ramon y Cajal S, Jones S, Vidal L, Shand N, Macarulla T, Ramos FJ, Dimitrijevic S, Zoellner U, Tang P, Stumm M, Lane HA, Lebwohl D, Baselga J. J Clin Oncol. 2008 Apr 1;26(10):1603-10.

A naturally occurring HER2 carboxy-terminal fragment promotes mammary tumor growth and metastasis. Pedersen K, Angelini PD, Laos S, Bach-Faig A, Cunningham MP, Ferrer-Ramón C, Luque-García A, García-Castillo J, Parra-Palau JL, Scaltriti M, Ramón y Cajal S, Baselga J, Arribas J. Mol Cell Biol. 2009 Jun;29(12):3319-31.

TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Peñuelas S, Anido J, Prieto-Sánchez RM, Folch G, Barba I, Cuartas I, García-Dorado D, Poca MA, Sahuquillo J, Baselga J, Seoane J. Cancer Cell. 2009 Apr 7;15(4):315-27.

Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon y Cajal S, Arribas J, Baselga J. J Natl Cancer Inst. 2007 Apr 18;99(8):628-38.

VHIO: empowering predictive cancer science towards rendering cancer therapies more precise

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VHIO strives to deliver the predictive data required to reliably inform the clinical development of innovative agents and approaches as well as evidence reproducibility before moving to the clinic:

VHIO has internationally renowned expertise in developing and finely tuning cancer models to identify factors influencing tumor growth, predict cancer progression and response to treatments, with one of the biggest PDX collections in Europe - particularly in breast, glioblastoma and colorectal cancers.


Current efforts include more accurately modeling anti-tumor immunotherapy strategies by generating humanized PDX models (Hu PDXs) to validate the efficacy of T-cell bispecific antibodies.

Using colorectal cancer PDX, VHIO groups have reported that Wnt inhibitors can overcome β-catenin-induced resistance to PI3K and AKT inhibitors and experimentally showed a rational stratification of patients to be treated with this trio of inhibitors using β-catenin and FOXO3A as predictive biomarkers of response. This marks a significant milestone in ultimately advancing personalized therapy against colorectal cancer.

Leadership in the generation of a variety of modelling systems including PDX and Organoids resulted in VHIO participating as a founding member of the EuroPDX Consortium.

One most recent example of VHIO's translational teams bringing discovery to market and clinical practice has been the validation of the RAD51 assay as predictive response biomarker of PARPi-clinical activity with implication beyond BRCA1/2-mutation carriers. This project is now supported by a technology transfer program to bring the RAD51 assay to market.

Predictive, translational and robust science of excellence at VHIO has also resulted in two spin-off successes.

To discover more about VHIO's Preclinical Research Program directed by Joaquín Arribas, ICREA Professor, click here

For developments reported by our Translational Research Program led by Joan Seoane, also an ICREA Professor, click here.

VHIO's novel programs and approaches in advancing anti-cancer armoury

VHIO's Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”: the hub of VHIO's early clinical drug development efforts focused on phase I and II trials with innovative agents and first-in-human studies:

Thanks to VHIO's translational vision, scientific framework, and its Prescreening Program, the Unit has established itself as one of the few comprehensive facilities in Europe to rapidly transform discovery into improved outcomes for patients.

Based on the idea that each tumor has an independent genetic identity, VHIO clinical scientists aim at potentiating molecular therapies targeting specific oncoproteins and accelerating more effective personalised cancer medicines for patients displaying genetic lesions or pathway dysregulation. One of the team's main objectives is to establish novel predictive markers of response to anti-cancer therapies and identify markers of primary resistance (de novo) and secondary treatment.

VHIO 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.

VHIO is also accelerating and advancing immunotherapies including atezolizumab, nivolumab and pembrolizumab.

VHIO continues to grow its portfolio of studies and fine-tune patient selection criteria and stratification based on intrinsic biological intelligence and a more precise classification of cancers. In 2017, 120 phase I clinical trials and 17 Basket studies were conducted with patient enrolment totaling at 445.

We have led the design of Cancer Core Europe Consortium-endorsed Basket of Baskets (BoB) trial. In 2017 the protocol for its first module was approved and first patient enrolment is envisaged towards the end of next year, 2018.

2017 celebrated the renewal of VHIO's framework program supported by the Fundació Bancària ”la Caixa”, in collaboration with the Memorial Sloan Kettering Cancer Center – MSKCC (New York), to further pursue the established synergies between the two.

To read more about VHIO's VHIO's Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, click here.

To discover more about VHIO's Clinical Research Program, led by Josep Tabernero, also Director of our Institute, click here.

VHIO: applying and extending immunotherapies to more tumor types

Driven by our Early Clinical Drug Development and Tumor Immunology & Immunotherapy Groups (led by Elena Garralda and Alena Gros repsecitvely), in collaboration with out teams at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, VHIO advances novel immune agents either as monotherapy or in combination:

Current research at VHIO pairs liquid biopsy with immunotherapy for the evaluation of patients treated with immune checkpoint inhibitors using novel sequencing technologies. Led by Enriqueta Felip (PI of our Thoracic Tumors & Head and Neck Cancer Group), in collaboration with Ana Vivancos (PI of our Cancer Genomics Group), research on the characterization of blood-based tumor-educated platelets for the analysis of these patients may more accurately guide immunotherapeutic strategies for the treatment of non-small cell lung cancer.


VHIO reported results from two early phase trials showing that the anti-CEA/CD3 novel bispecific antibody, either as monotherapy or paired with atezolizumab, promises an increased therapeutic efficacy in the treatment of metastatic colorectal cancer. Its effect also proved more potent in combination.

UITM's Task Force - incorporating VHIO's scientists and clinical investigators in early drug development of immunotherapeutics and cell signaling centers on second generation immunotherapies, including new cytokines, immunomodulatory agents and immune checkpoint inhibitors and combinations, as well as translational research in immuno-oncology.

Regarding the aforementioned BoB trial (sub-section 'Cancer Core Europe'), the first module to open will focus on the response of tumors to anti-PDL1 therapy based on mutation load and DNA repair status.

Launched by Roche in 2016, the Immunotherapy Centres of Research Excellence (imCORE) Network is a global partnership powered by 25 leading cancer research institutions, including VHIO. This network is driving the application and extension of novel immune-based medicines to more tumor types as well as progressing research into the cellular and molecular mechanisms modulating immune response to cancer.

In 2017 VHIO and the BBVA Foundation (Fundación BBVA), this year renewed their research program in collaboration the Memorial Sloan Kettering Cancer Center - MSKCC (New York). Building on the successes 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.

For more information about our Early Clinical Drug Development Group click here. To discover more about our Tumor Immunology & Immunotherapy Group click here.

VHIO and the power and potential of cancer subtyping

To deliver transformative therapies VHIO validates molecular subclasses of disease and better develops, matches, and measures novel therapies according to the specificities of each molecular subtype: Led by Rodrigo Dientstmann (PI of our Oncology Data Science - ODysSey - Group), VHIO has co-established a novel classification for colorectal cancer based on genomic and transcriptomic data. We led efforts to establish 4 main molecular subtypes evidenced by consensus. These data promise a more precise prognosis and will better predict response to targeted molecular therapies as well as guide more precise therapeutic strategies.

Genomic technologies, cutting-edge platforms, coupled with big data generated by international networks and collaborations, including the Horizon 2020-supported MoTriColor which is led by VHIO, are enabling us to accelerate the translation of molecular subclasses and biomarkers into benefits at patient level.

As a reflection of our expertise, VHIO has just been accepted to participate in the American Association for Cancer Research's (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE).

For more updates on these important efforts in 2017 click here to see our Oncology Data Science Group, click here.

Oncogenomics and VHIO's Prescreening Program

VHIO is one of the few centres in Europe to run such a comprehensive prescreening program: molecular profiling in around 1500 patients per year as candidates for enrollment in our Research Unit for Molecular Therapies of Cancer (UTIM) - ”la Caixa” early phase trials. This enables VHIO to more precisely match an increasing number of individual patients with a particular study. This program is pioneered by Ana Vivancos in collaboration with Paolo Nuciforo, PIs of our Cancer Genomics and Molecular Oncology Groups, respectively:

Enabling technologies: VHIO applies state-of-the-art technologies for precision oncology and develops existing applications for faster results (n-counter Nanostring platform, BEAMing Sysmex, and Droplet Digital PCR (ddpCR) Bio-Rad Technology, Miseq and HiSeq2500, Illumina).

Two of these tests are based on NGS: an Amplicon-seq approach to sequence 70 genes (Illumina), as well as a 400-gene capture panel, and two are based on nCounter (Nanostring): a gene fusion panel (with the capacity of detecting over 100 recurrent gene fusions) and a Copy Number Alteration panel (detecting 59 genes).

Since we are able to develop and perform high quality testing on patient samples, VHIO is increasingly approached by the pharmaceutical industry and other research entities as either the selected Central Lab of choice, or as their preferred service provider and advisor.

VHIO's main testing methods continue to successfully undergo ISO 15189 accreditation – reflecting excellence and quality.

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VHIO's suite of enabling technologies

For more updates in 2017 click here. To find out more about our Cancer Genomics and Molecular Oncology Groups, click here

The power of collaboration of excellence: at home and away

VHIO believes in combining strengths and overcoming current challenges in concert, and consequently (co) identifies, develops and cements alliances globally. As is widely document throughout this Report, in order to help accelerate efforts aimed at solving cancer sooner, VHIO is called upon to lead and co-participate in many pan-European and international collaborations and consortia of excellence.

‘At home’ to further reinforce VHIO's purely translational and multidisciplinary model, we continue to expand our expert and interdisciplinary taskforces, as well as foster and support strategic alliances between public entities across Catalonia.

VHIO-born entrepreneurship

2014 celebrated the launch of two Spin-Off successes:

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VHIO research establishing the role of leukemia inhibitor factor (LIF) as a promoter of cancer progression and the discovery of humanized antibody MSC-1's capacity to effectively target LIF, led to the launch of VHIO-born spin-off Mosaic Biomedicals S.L., and the promise of the accelerated clinical development of MSC-1.

Co-founded by our Director of Translational Research and ICREA Professor, Joan Seoane, Mosaic merged in 2016 with a Canadian company, Northern Biologics, and will run a clinical trial across sites at VHIO, Memorial Sloan Kettering Cancer Center (MSKCC), and the Princess Margaret Hospital in early 2018.

In 2017 the company was co-recipient of CataloniaBio's Biosuccess Award of the Year for its exceptional entrepreneurship and biobusiness development aimed at advancing healthcare. This year's prize recognized the aforementioned merger the consequent promise of the humanized antibody MSC-1.


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Built on research carried out at VHIO to successfully translate Omomyc-based therapy into clinical application, a second VHIO spin-off, Peptomyc S.L., co-founded by VHIO's Laura Soucek in 2014 (PI of our Mouse Models of Cancer Therapies Group, ICREA Professor, and CEO of this company, centers on developing anti-Myc peptides for the treatment of non-small cell lung cancer, triple negative breast cancer and glioblastoma. The Omomyc cell-penetrating peptide (CPP), proven preclinically, promises to become the first ever clinically viable and direct inhibitor of Myc – a protein implicated in the formation of most tumor types.

In 2017 this spin-off secured 4.2 million euros in a Series A round led by the Barcelona-based venture capital investment firm, Alta Life Sciences. This funding will provide Peptomyc with the necessary capital for the development of clinical trials to test this novel peptide for the inhibition of MYC.



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Recognition through accreditation

In 2017 VHIO underwent evaluation for accreditation of the CERCA Institute of Research Centres of Catalunya (Institució CERCA – Centres de Recerca de Catalunya) for the period 2013 – 2016. In recognition of VHIO's progress, performance in knowledge transfer activities and management of excellence, VHIO was awarded with the maximum qualification of an A grading.

Also reflecting our dedication to excellence and the quality of our services and procedures, our Cancer Genomics and Molecular Groups, led by Ana Vivancos and Paolo Nuciforo respectively, have both received ISO 15189 accreditation for their testing methods and technologies. Similarly, we continue to meet the high standards in quality and procedures in the audit of our clinical trials Units, carried out by the Generalitat de Catalunya. Our Research Management is also endorsed by ISO 9001 Certification.



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Dr. Pere Mir
Founder and President, Fundació Privada CELLEX
(1919 – 2017)


“I am truly grateful to Dr. Pere Mir for his immeasurable generosity and backing and belief in biomedical research across Catalonia. He was a remarkably kind human being, a true gentleman and scholar. He is sorely missed by us all.”

Josep Tabernero,
Director of VHIO.

In Memorandum

2017 sadly marked the passing one of the greatest supporters of biomedical research and healthcare across Catalonia, Dr. Pere Mir, Founder and President of the Fundació Privada Cellex.

The many initiatives that have been fortunate enough to benefit from Dr. Mir's conviction and thus, funding from CELLEX, include VHIO, the Vall d'Hebron University Hospital, Institute of Photonic Sciences (ICFO), IDIBAPS Institute of the Hospital Clínic, other leading hospitals across Catalonia, as well as the Centro de Formación Interdisciplinaria Superior (CFIS).