FOREWORD by VHIO's Director Josep Tabernero

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INTRODUCING VHIO
Who we are and what we do

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VHIO in 2018: myriad highlights and new horizons

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FOREWORD by VHIO´s Director Josep Tabernero

VHIO in 2018: myriad highlights and new horizons
Josep Tabernero
Director, Vall d'Hebron Institute of Oncology (VHIO)

This year’s Vall d’Hebron Institute of Oncology’s (VHIO) Scientific Report branding features the infinity symbol. Indeed, flipped on its head it is of course a number 8 in celebration of VHIO embarking on its second decade ahead.

For me, this symbol represents much more than a concept or a figure. Rather, it depicts a virtuous cycle of knowledge; the seamless and unrestricted flow of discovery in oncology from the bench to the bedside and back. It is also illustrative of the multidisciplinary and translational research model for which VHIO is famed.

As I reflect on the past year and consider the current state of oncology within the broader context of precision medicine, the progress we are collectively making to solve cancer sooner is undeniably great.

At the research level, thanks to the past decade’s increased focus on prevention and early diagnosis, as well as the expanding portfolio of potent anti-cancer medicines matched to molecular signatures of individual tumors, we continue to translate progress into proven benefits for our patients.

These successes have been driven, in parallel, through the rapid development of omics platforms and prescreening tests, the better harnessing, sharing and interpretation of big data, and novel treatment approaches.

The recent addition of promising immunotherapeutics to the arsenal of anti-cancer weaponry, coupled with circulating tumor (ct)DNA analysis for more predictive tracking of disease, are helping us to deliver on the true promise of personalized medicine in oncology.

As Director of VHIO, it is both a privilege and pleasure for me to mention just some of the many important contributions driven by our research teams in 2018, often in partnership with colleagues across the globe as well as pioneering international consortia.

These exceptional advances and developments in cancer science and medicine will help us to collectively up the tempo in more effectively reversing cancer resistance and halting metastatic cell spread, in ’real time’, on time.

Let’s dig into a few of the myriad VHIO highlights over this past year:

Cancer modelling, predictive biomarkers and the unmasking of novel drug-targets: three jewels in VHIO’s crown

Empowering predictive and reproducible cancer science

At VHIO, we are dedicated to accelerating robust preclinical data required to reliably guide the clinical development of innovative agents and approaches, as well as evidence its reproducibility before moving into the clinic.

An area of strength is in cancer modelling, with particular emphasis on tuning patient-derived xenograft (PDX), avatar and organoid models to identify factors governing tumor progression and response to therapy. VHIO is both a founding member and sits on the Board of Coordinators to steer strategic directions of the EurOPDX Consortium–Translating Knowledge in Oncology (launched in 2013).

Announced in 2018, the EurOPDX partners secured funding from the EU’s Horizon 2020 research and innovation programme to construct a repository for the open access sharing of more than 1500 established PDX models, complete with their clinical, molecular and pharmacological annotations: EDIReX–EurOPDX Distributed Infrastructure for Research on patient-derived cancer Xenografts.

Coordinated by Enzo Medico, Candiolo Cancer Center IRCCS (Turin, Italy), this platform counts on the research excellence of 19 entities spanning 13 European countries, including VHIO.

With one of the biggest PDX collections in Europe, particularly in breast, glioblastoma and colorectal cancers, we will assume a leading role in strengthening this essential open access resource. In addition, as we strive to more accurately model immunotherapy strategies through our generation and development of humanized PDX to validate the performance of T-cell bispecific antibodies, our research promises to reveal precious insights that we will be sharing via this exciting new platform (see sub-section, Immunotherapy: hope v’s the over-hyped, in this Foreword).

A second pan-European undertaking fueled by EU’s Horizon 2020, MESI-STRAT will establish the interplay of breast cancer metabolism and oncogenic signaling by systems medicine approaches. Co-coordinated by Kathrin Thedieck, University Medical Center Groningen (The Netherlands), and Tobias Anzeneder, PATH Biobank (Munich, Germany), this consortium combines the expertise of 14 partners including VHIO. It centers on breast cancer metabolism as a novel approach for the stratification of patients, tracing resistance, and better informing clinical decision-making throughout the course of endocrine therapy.

VHIO’s library of in vitro and in vivo models will provide data required to individualize and validate MESI-STRAT’s computational models. Violeta Serra, PI of our Experimental Therapeutics Group, will help to develop metabolite marker panels to guide established targeted therapies for the treatment ER-positive tumors that are resistant to endocrine therapy.

Coordinated by Cristina Saura, PI of VHIO’s Breast Cancer & Melanoma Group, we will also interrogate the predictive value of specific biomarkers in liquid biopsies from patients enrolled in our clinical studies with novel therapies.

Busted: exposing new drug-targets

A study (1) published in The Journal of Clinical Investigation, led by PI of our Stem Cells & Cancer Group, Héctor G. Palmer, in collaboration with several other VHIO groups, revealed a novel drug-target to ‘strangle’ sleeper cancer cells.

Their findings have evidenced an epigenetic enzyme, TET2, as a biomarker to identify dormant tumor cells (DTC), also known as slow-cycling cancer cells (SCCC), which go undetected by current treatments that have mostly been designed to target rapidly dividing tumor cells.

Having secretly travelled and settled in other parts of the body, when DTC awake they behave like cancer stem cells, regenerate the original tumor and drive metastasis in patients thought to be cured.

Palmer and colleagues identified TET2 as the Achilles heel of dormant tumor cells and also sought to develop novel inhibitors aimed at preventing their seeding of metastasis. By establishing that TET activity correlates with elevated levels of 5hmC as well as a greater risk of resistance to therapies and disease relapse, these insights into the molecular intricacies of DTC provide a promising translational opportunity toward potentiating treatments, preventing cancer recurrence, and extending the survival of patients.

Teaching an old protein new tricks, research headed by Josep Villanueva, PI of our Tumor Biomarkers Group, in collaboration with the CIBERONC Center for the Biomedical Research Network in Oncology (scientifically led by VHIO’s Joaquín Arribas, Co-Director of our Preclinical and Translational Research Program), has unmasked extracellular HMGA1 as a novel drug target for the treatment of metastatic triple-negative breast cancer (TBNC) and a predictive biomarker of cancer cell spread.

By elegantly reporting the correlation between HMGA1 secretion and its nucleus-to-cytoplasm migration in Clinical Cancer Research (2), these important insights change the view on this protein’s role in tumorgenesis, and support the relevance of unconventional protein secretion in cancer diagnostics and therapeutics.

Led by our Mouse Models of Cancer Therapies Group, directed by PI Laura Soucek, a study published in Oncotarget (3) offers preclinical evidence for the role of a novel BET inhibitor in more effectively treating Kras-driven cancers.

Their results in mouse models of Kras-mutated pancreatic ductal andenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) support the further evaluation of BET inhibition in solid tumors in the clinic. Future directions will need to focus on how to potentiate the blocking of BET either as monotherapy or in combination with other drugs, as well as reduce the toxicity reported in some early clinical studies.

Another VHIO contribution to the science of cancer progression this year was reported in Nature Communications (4) by Sandra Peiró and her Chromatin Dynamics in Cancer Group. They showed that the inner nuclear protein, lamin B1, is necessary for the 3D genome rewiring required to transform an epithelial cell and enable it to migrate and invade other tissues.

By reducing levels of this protein, her team showed that by effectively eliminating part of it, the cells lose their ability to become mesenchymal stem cells, thus reducing their capacity to travel and relocate. These findings represent another forward step towards better understanding the drivers of disease spread.

Powerful blows against BRCA1/2 mutated disease

Speaking of drug-targeting, in our determined pursuit to establish more effective treatment strategies that target vulnerabilities in BRCA1/2-associated cancer, my first selection are the results from the phase III SOLO-1 multi-center trial led by Kathleen Moore, Stephenson Cancer Center (Oklahoma, USA), and co-authored by Ana Oaknin who leads our Gynecological Malignancies Group.

Selected to first outing at the 2018 ESMO Congress (19-23 October, Munich, Germany), during the Presidential Symposium that I co-chaired and timed in parallel to publish in The New England Journal of Medicine (5), data showed that treatment with olaparib maintenance therapy led to a spectacular extension of progression-free survival by 3 years in over 50% of patients with newly diagnosed advanced ovarian cancer. This pivotal study also revealed that this novel treatment approach reduced the risk of disease progression by an impressive 70%.

Judith Balmaña’s Hereditary Cancer Genetics Group, in collaboration with our Breast Cancer & Melanoma (PI Cristina Saura), and Experimental Therapeutics (PI Violeta Serra,) Groups co-authored a paper in The Journal of Clinical Oncology (6) from a USA-Spanish multicenter phase II trial that signposts new direction in the treatment of BRCA1/2 mutated advanced breast cancer.

Blocking transcription and induces DNA double-strand breaks leading to apoptosis, they have proposed the novel agent lurbinectedin as a potentially more powerful therapy against this tumor type. Importantly, this research also included a translational sub-study assessing potential mechanisms of resistance to this promising inhibitor. These important findings were covered in a news review published by The Lancet Oncology (7).

At the preclinical and translational level, research led by Violeta Serra, in collaboration with the other VHIO groups mentioned in my previous highlight, among others, culminated in two publications (8) (9), this year that provided important new insights into resistance and response to PARPi both in BRCA-mutated breast cancer and beyond.

This year the group developed their RAD51 foci assay, PARPiPRED, which accurately identifies germline BRCA tumors that have restored functionality, as well as other tumor types that are sensitive to these inhibitors. Importantly, they have also shown that this test is both feasible in routine tumor samples and a simple technique to apply.

While we hope for ease and speed in its translation to the clinic, further studies are now underway to more precisely define the sensitivity and specificity of PARPiPRED in predicting PARPi benefit and thus more informed patient selection.

Immunotherapy: hope vs the over-hyped

The promise and performance of novel immunotherapies (not to mention the price tags of those approved to-date) have once again been under intense scrutiny this year, with several editorials and opinion pieces, including one by The Lancet Oncology (10), calling for an adjusted alignment of expectations with current realities.

I also touched on this in an editorial that I was invited to pen for ESMO Open (11) to mark the mid-term of my Presidency of the European Society for Medical Oncology.

The emergence of these novel drug contenders should be celebrated, but much work still needs to be done to better predict those patients who would most likely benefit from them, extend their early promise to more patients as well as tumor types–either as monotherapy or, most likely, in combination, and tackle important concerns regarding safety and toxicity.

While immunotherapies are largely not yet benefiting as many patients as they promise, I believe that we are on the cusp of change. I am not alone: at the close of the year, several reports in the specialized and general media including Forbes (12) magazine as well as the official blog of the American Association for Cancer Research (AACR), CANCER RESEARCH Catalyst (13), predicted great things to come in 2019.

This will only happen by extending our efforts aimed at potentiating and personalizing this armory to successfully unleash the power of the immune system in a greater number of individu als to attack disease. We must deliver the robust immune data required to better guide treatment decisions that benefit all patients and not just the so-called ‘super-responders’.

VHIO continues to lead cancer discovery in this direction. Our preclinical research culminated in a publication in Science Translational Medicine (14), showing that a decade-old protein, p95HER2, previously described by VHIO, offers a target for novel therapy that steers the immune system to hone in on and eliminate tumor cells.

Findings reported by our Growth Factors Group, led by Co-Director of Preclinical & Translational Research at VHIO and ICREA Professor, Joaquín Arribas, revealed that p95HER2-T cell bispecific antibody (TCB), enables a targeted response by attacking cancer cells directly without affecting normal ones.

Thanks to the distinct specificity of TCB and this particular protein’s exclusive location in malignant cells, the authors have described a ‘home-delivery’ of immune-based therapy. Approximately 10% of patients with HER2-positive breast cancers expressing p95HER2 could ultimately stand to benefit from this novel strategy.

Having now completed the preclinical phase of development, Joaquín’s team is now focusing on advancing this therapy so that it can be administered in patients enrolled in clinical trials. Next steps will also include developing additional therapies against p95HER2 such as antibody-drug conjugates or chimeric antigen receptors (CARs).

I am excited to report our Experimental Hematology Group, directed by Francesc Bosch is participating in the first international, multi-center phase II clinical trial, TRANSCEND World, to assess the efficacy of chimeric antigen receptor (CAR) T cell therapy for patients with aggressive B-cell non-Hodgkin lymphoma. We are the first Spanish site to conduct a CAR T cell clinical study in this population and also the first to have been granted authorization for patient enrolment.

In collaboration with an additional 15 selected sites across Europe as well as two in Japan, this study has been designed to determine the efficacy and safety of JCAR017 to treat clinically selected adult patients with relapsed or refractory disease. The investigators will seek to validate the promising response rates and superior profile of this immunotherapy observed in early phase trials.

A paper (15) in The New England Journal of Medicine, co-first authored by Enriqueta Felip who leads our Thoracic Tumors & Head and Neck Cancer Group, showed promise for the more effective treatment of patients with metastatic non-small-cell lung cancer (NSCLC). Results from a phase II study reported that treatment with pembrolizumab paired with chemotherapy led to higher rates of response as well as longer progression-free survival than with chemotherapy alone.

This study exemplifies the progress that we are making by empowering immunotherapeutics in combination with the cornerstones of cancer therapy–chemotherapy, surgery and radiation. We are also better understanding the cellular and molecular mechanisms modulating immune response and learning from the outcomes of immune-based clinical trials.

Flanking our other research programs and priorities, the Obra Social ”la Caixa” International Program for Cancer Research and Education, as well as the BBVA Foundation’s Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), represent pioneering research endeavors aimed at delivering on the true promise of this array of novel ‘immunoarmory’ in oncology.

Guiding treatment decision making through novel approaches, platforms and scales

Liquid biopsies: ready for prime time?

At the preclinical and translational level, VHIO was the first academic test center to incorporate in-house BEAMING liquid biopsy RAS biomarker technology (2015). We have since made significant progress in validating and developing liquid biopsy technologies for the more effective, less invasive monitoring of cancer in real time.

These efforts, focused on both ctDNA and tumor educated platelets (TEP), continue to advance thanks to our multidisciplinary teams in collaboration with our two of VHIO’s core facilities, our Cancer Genomics and Molecular Oncology Groups headed by Ana Vivancos and Paolo Nuciforo, respectively.

This year, Joan Seoane, Co-Director of our Preclinical and Translational Program, also an ICREA Professor, was the corresponding author of a paper published in Clinical Cancer Research (16), showing proof-of-concept that cerebrospinal fluid (CSF) can be exploited for liquid biopsies as it contains ctDNA.

Carried out in collaboration with other researchers and clinical investigators at VHIO, as well as oncologists, pathologists and neurosurgeons across the Vall d’Hebron Barcelona Hospital Campus, this study has not only unmasked the molecular characteristics of diffuse gliomas but also promises a more precise and rapid diagnosis that could help steer treatment decision making matched to the classification of these tumors, as well as more closely monitor the course of disease and response to therapy.

Ready for prime time? Not quite. My caution is echoed in a superb commentary in Annals of Oncology (17), authored by Ana Vivancos, with co-contributors, Elena Élez, Clinical Investigator and Molecular Oncologist of our Gastrointestinal & Endocrine Tumors Group led by Teresa Macarulla, and Ramón Salazar, Catalan Institute of Oncology – ICO.

Reviewing a study (18) in Annals of Oncology led by Jakob Vasehus Schou, Department of Oncology, Herlev & Gentofte Hospital, Copenhagen (Denmark), the authors concluded that several issues including timing, simplicity, time to results and cost-effectiveness should all be tackled when considering ctDNA liquid biopsy in the routine testing in cancer patients. They call for clinical trials to bring this exciting technique even closer to the clinic.

Based on the collective body of evidence, coupled with the tremendous progress thus far, I believe this goal is well within reach.

Facilitating the in-depth, accelerated interpretation of cancer genomes

At the core of VHIO’s research activities lies our suite of cutting-edge core technology platforms, which provide our teams with the necessary expertise to apply next-generation whole-genome sequencing for precision oncology as well as develop and improve existing applications to drive faster results.

Our prescreening program, powered by VHIO’s Cancer Genomics and Molecular Oncology Groups, led by Ana Vivancos and Paolo Nuciforo respectively, performs molecular profiling in more than 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.

Two of VHIO’s guiding principles are team science and the open exchange and sharing of data to accelerate precious insights in oncology. This has resulted in numerous cross-border alliances and partnerships; several in the form of international consortia, others in novel platforms, programs as well as value framework tools.

Our Oncology Data Science (ODysSey) Group directed by Rodrigo Dienstmann, is dedicated to interpreting and exchanging meaningful mass data in oncology.

As a reference in driving ‘big’ data-derived insights and exploring molecular profiles to more precisely guide treatment decisions, VHIO was invited to participate the American Association for Cancer Research’s (AACR) Project GENIE: Genomics Evidence Neoplasia Information Exchange.

I am proud to report that VHIO is the only GENIE member from Spain, selected for our expertise in better identifying and describing the clinical relevance of driver genomic alterations that trigger cancer.

Rodrigo has pioneered the design of several open access online tools to help physicians and investigators interpret genomic data and apply this knowledge in practice. Published this year in Genome Medicine (19), Rodrigo and VHIO’s Ana Vivancos co-authored a paper describing the Cancer Genome Interpreter (CGI) platform.

Led by ICREA Professor Nuria Lopez-Bigas, Institute for Research in Biomedicine (IRB, Barcelona), CGI represents an important step in providing the scientific community with access to this data in a more structured, consolidated and user-friendly way.

Speaking of cancer classification, 2018 celebrated the launch of the European Commission Horizon 2020-supported project led by Annette Byrne, Royal College of Surgeons in Ireland (Dublin), powered by 14 partners, including VHIO: COLOSSUS–Advancing a Precision Medicine Paradigm in metastatic Colorectal Cancer: Systems based patient stratification solutions.

Set to simplify and standardize choices for the selection of targeted cancer therapies, the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) published in Annals of Oncology (20).

Led by Joaquin Mateo, Principal Investigator of our Prostate Cancer Translational Research Group, also co-authored by Rodrigo Dienstmann, this new tumor DNA scale classes alterations according to their relevance as markers for the selection of patients matched to targeted treatments, based on the strength of clinical evidence.

Importantly, this new grading system will help guide physicians to distinguish between the genetic alterations that are important for treatment decisions or access to clinical trials, and those which are not.

The Last Word

While the important advances described so far (and more to follow) are gratifying, there is much more work to be done.

Due to late-stage diagnosis, metastatic cell spread, drug resistance and disease relapse, treatment options for an unacceptable number of patients are anything but limitless. They are finite, as seen in the daunting global cancer data.

Recently published statistics in the GLOBOCAN 2018 database (21) report that the cancer burden rose to 18.1 million new cases and 9.6 million cancer deaths in 2018. Additionally, cancer cases are forecast to rise by 75% over the next two decades.

While we can be optimistic that personalized medicine in oncology is starting to happen in practice, we still have far to travel if we are to extend our successes in cancer research to an increasing number of our patients.

VHIO’s talents can only continue to do so thanks to the precious funding received from our treasured institutional supporters–the Generalitat de Catalunya, Fundació Privada CELLEX, FERO Fundación de Investigación Oncológica, Fundació Bancària ”la Caixa”, Fundación BBVA,, as well as our many other supporters, funding entities and agencies.

Year in, year out, VHIO’s preclinical, translational and clinical teams work tirelessly to broaden the array of more effective treatments and enabling technologies tailored to the specificities of individual patients. Importantly, we also do so in collaboration.

I believe in forging essential collaborations with other specialties and partners. We can only continue to tackle the current challenges that are impacting on our ability to more rapidly advance precision medicine against cancer together.

I am confident that we can collectively turn obstacles into opportunity and optimal outcomes for all stakeholders in oncology. Above all, we must continue to listen and respond to the needs of those who matter most–our patients.

As VHIO embarks on its second decade ahead, I am confident that we can, and will, do even better.

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


References
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INTRODUCING VHIO

Who we are and what we do

VHIO's Organigram 2018

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:

VHIO organigram

VHIO in 2018: myriad highlights and new horizons

VHIO's translation toward precision oncology: a little more on how we did it in 2018

Under the leadership of Josep Tabernero, the Vall d’Hebron Institute of Oncology (VHIO), created in 2006, has established itself as a comprehensive cancer centre of proven excellence internationally. It is thanks to the devotion of our Principal Investigators and their teams, coupled with 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.

That said, our Institute would cease to exist without the generous support it receives from its Institutional Supporters, public funding, private institutions, companies, and individuals, as well as International and National Competitive Grants.

Special mention here highlights the tremendous belief and backing that we continue to receive from our dedicated patrons: the Generalitat de Catalunya, Fundació Privada CELLEX, FERO Fundación de Investigación Oncológica, Fundació Bancària ”la Caixa”, and Fundación BBVA.

Just some of their respective, major contributions include the following:


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

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

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

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

As an active member of the CERCA Institute of Research Centers of Catalonia (Institució CERCA–Centres de Recerca de Catalunya), this collaboration affords us access to the Catalan Research System and the fiscal and legal benefits that this represents.

The financial support it has provided has consequently contributed majorly to VHIO’s structural overheads, allowing us to center our efforts on our core research activities.


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

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

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

Providing the valuable space through which to grow, the CELLEX Center has not only further enhanced collaborations and accelerated our dedicated efforts to combat cancer, it has also allowed us to expand our groups in order to pursue new emerging research areas including immunology & immunotherapies, as well as fortify our research structure.

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


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Support received from the Fundación FERO (FERO Foundation), has, from the very beginning, enabled science of excellence at VHIO as well as promoted the careers of up-and-coming talents in oncology through its annual Fellowships. Concerning the former, the labs of Josep Villanueva, PI of our Tumor Biomarkers Group, Laura Soucek, PI of VHIO’s Mouse Models of Cancer Therapies Group and ICREA Professor, Violeta Serra, PI of VHIO’s Experimental Therapeutics Group, Joaquín Arribas, Co-Director of our Preclinical and Translational Program and ICREA Professor, who also heads our Growth Factors Group, and Sandra Peiró, who leads our Chromatin Dynamics Group, have been able to grow their groups and advance their pioneering research lines thanks to FERO.

Regarding its Annual Award for Translational Research, a total of seven of our research scientists have been honored with this prize: Laura Soucek (2011), Héctor G. Palmer (2012), Ibrahim Yasir – formerly an investigator of VHIO’s Experimental Therapeutics Group directed by Violeta Serra (2013), César Serrano (2015), Beatriz Morancho (2016), María Abad (2017), and Alena Gros (2018).

FERO has also contributed to the expansion of our facilities. As an example, the Foundation was a sponsor of our Breast Cancer Center “Endavant i de Cara“, along with a personal donation received from Maria Angels Sanahuja. Funding received from FERO also enables us to develop our Droplet Digital PCR (ddpCR) Bio-Rad Technology platform and advancing research into the more effective and less invasive tracking of cancer by liquid biopsy.


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Thanks to the support received from our private patron, the Fundació Bancària ”la Caixa” (”la Caixa” Foundation), VHIO’s Research Unit for Molecular Therapies of Cancer (UITM) – ”la Caixa” opened its doors in 2010 to pioneer early drug discovery and clinical studies tailored to the specificities of patients.

This Unit, under the co-direction of Josep Tabernero and Elena Garralda, has subsequently established itself as a leading reference in developing novel therapies based on the molecular profile of each tumor and optimize treatment strategies using combinations of new agents with already existing ones.

Furthermore, in addition to various grants supporting several VHIO groups, this Foundation also fuels one of our two major institutional programs: Obra Social ”la Caixa” International Program for Cancer Research and Education.


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Also driving programs to spur VHIO’s avant-garde translational research in precision oncology, another of our private patrons, Fundación BBVA (BBVA Foundation), financed our Tumor Biomarkers Research Program back in 2011. This five-year major framework agreement fueled collaborative science centering on the development of personalized therapies for cancer patients through biomarker research.

Building on the successes of this first program, our second BBVA-VHIO Institutional Program: the BBVA Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), represents an important forward step in advancing agents that inhibit checkpoint regulation of the immune system, better understanding mechanisms of resistance and response to these therapies, and prioritizing the early development of those drugs showing most promise. It also supports various research lines across other VHIO groups. Leading these research efforts are Alena Gros and Elena Garralda, PIs of our Tumor Immunology & Immunotherapy and Early Clinical Drug Development Groups, respectively.


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

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.


Principal areas of cancer research at VHIO: at a glance

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

Driving and applying powerful technology platforms

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

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

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

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

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

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

Another two are based on nCounter (Nanostring). The gene fusion panel, with the capacity of detecting over 100 recurrent gene fusions, is also enabling us to assess gene expression patterns in tumors. Copy Number Alterations are evaluated with a 59 gene panel for genes with frequent gains or losses in cancer. Reflective of excellence and quality, they have attained ISO 15189 flexible accreditation for the Amplicon-seq testing method.

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

At the preclinical and translational level, VHIO was the first academic test center to incorporate in-house BEAMING liquid biopsy RAS biomarker technology (2015). We have since made significant progress in validating and developing liquid biopsy technologies for the more effective, less invasive monitoring of cancer in real time.

These efforts, focused on both ctDNA and tumor educated platelets (TEP), continue to advance thanks to our multidisciplinary teams in collaboration with VHIO’s Cancer Genomics and Molecular Oncology Groups. As an example, as updated by our Director in his Foreword, Joan Seoane, Co-Director of our Preclinical and Translational Program and ICREA Professor, and colleagues showed proof-of-concept that cerebrospinal fluid (CSF) can be exploited for liquid biopsies as it contains ctDNA.


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

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

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

Research at the UITM is driven by Elena’s Early Clinical Drug Development Group, and focuses on the development of novel agents based on the molecular profile of each tumor as well as the optimization of therapies using combinations of new drugs with existing ones.

In 2018, our Unit participated in 161 ongoing phase I clinical trials, 22 of which were Basket trials. Our facilities, coupled with our multidisciplinary clinical teams, enable us to continue to expand our portfolio of phase I studies. This year we opened 51 new trials; 4 as Baskets. 508 patients were recruited, 64 of whom were enrolled in Baskets. Our Clinical Trials Office, directed by Gemma Sala and also located in the patient environment of the Vall d’Hebron University Hospital (HUVH), coordinates a large portfolio of Phase I, Baskets, Phase II & III clinical trials. In 2018 the number of patients included in these trials totaled at 1198 across 399 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.

Speaking of novel immunotherapeutics, our Unit’s Taskforce spearheads the early drug development of these agents and cell signalling. Specifically, we focus on second generation immunotherapies, including new cytokines, bispecifics, immunomodulatory agents and immune checkpoint inhibitors and combinations, as well as translational research in immuno-oncology in collaboration with several VHIO groups.


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

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 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.


Championing research aimed at solving cancer sooner

2018 celebrated a record breaking year in terms of the impact of our cancer science. 282 scientific articles were published by VHIO researchers as corresponding/senior or co-authors with a cumulative Impact Factor (IF) totalling at 3501.

This figure reflects an increase in the importance of VHIO’s contribution to the oncology field. For the complete list of articles published by VHIO researchers and clinical investigators in 2018 click here.


Delivering on the promise of novel immunotherapies

As cautioned by our Director in his Foreword, while the emergence of these novel drug contenders are showing promise in the treatment of an increasing number of tumour types, much work still needs to be done if we are to collectively extend their early promise to more patients and seek out ways to potentiate and better personalize these agents and, in parallel, tackle important concerns regarding safety and toxicity.

In addition to the aforementioned research pioneered by our clinical programs, VHIO is also advancing this field at preclinical and translational level.

A bispecific antibody against p95HER2 guides cells of the immune system to malignant cells. Pink cells represent healthy breast epithelial cells, brown cells represent malignant cells. Only malignant cells express p95HER2 (in blue), which is recognized by the p95HER2 bispecific antibody which, in turn, guide lymphocytes form the immune system of the patients (blue cells), against the tumor cells.

As an example in 2018, research led by Joaquín Arribas, Co-Director of Preclinical and Translational Research at VHIO, and ICREA Professor, revealed a target for novel therapy that steers the immune system to hone in on and kill tumor cells.

Among the many other immune-based VHIO studies and approaches that feature throughout the pages to follow, Josep Tabernero selected two other illustrative examples as part of his Foreword’s sub-section Immunotherapy: hope vs the over-hyped.

Led by Francesc Bosch, PI of our Experimental Hematology Group,VHIO is the first Spanish site to conduct a CAR T cell study to assess the efficacy of this therapy in patients with aggressive B-cell non-Hodgkin lymphoma, as part of The TRANSCEND World multi-center phase II clinical trial.

An additional pick for this year’s highlighted research was spearhead by Enriqueta Felip, who leads our Thoracic Tumors and Head & Neck Cancer Group, which showed promise for patients suffering from metastatic non-small-cell lung cancer. Specifically, results from a phase II clinical trial showed that combining pembrolizumab with chemotherapy led to higher response rates and longer progression-free survival than with chemotherapy alone.

Set to significantly impact on our ongoing research efforts focused on advancing immunotherapies against cancer, are our two institutional programs supported by our private patrons, Obra Social ”la Caixa” and the Fundación BBVA:


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

Aimed at pioneering collaborative projects co-led by VHIO and the Memorial Sloan Kettering Cancer Center – MSKCC (New York, USA), the Obra Social ”la Caixa” International Program for Cancer Research and Education renewed as a second initiative in 2017 to consolidate and further pursue the established synergies between the two leading institutions.

This second edition, co-directed by Josep Tabernero and Maurizio Scaltriti (MSKCC), will include several initiatives focused on the pan-omic exploration (genomics and radiomics) of solid tumors, with particular emphasis on Big Data analysis, coupled with clinical insights from real-life patients.

Driven in collaboration with several VHIO groups, one of the three projects currently underway is dedicated to radiomics and immunotherapy. The other two focus on the impact of gene mutations in DNA damage on the impact of gene mutations in DNA damage repair and metastatic prostate cancer, and Big data mining to uncover molecular and genetic determinants of sensitivity to targeted therapy in solid cancers.

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

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

Building on the achievements of the first program, the BBVA Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), represents an important forward step in advancing agents that inhibit checkpoint regulation of the immune system, better understanding mechanisms of resistance and response to these therapies, and prioritizing the early development of those drugs showing most promise.

Under the leadership of Josep Tabernero, this ambitious undertaking counts on the expertise of several clinical and translational VHIO groups, and has launched six translational sub-projects linked to the early clinical development phases of immunotherapy. These pioneering research endeavors are currently underway.

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Potentiating our programs in partnership: at 'home' and away

Accelerating precision medicine through 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 ten groups covering colorectal, breast, lung, gynecologic, prostate, melanoma, pancreatic, gastric tumor types as well as immunotherapy and onco-imaging, 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.

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VHIO’s task-forcing teams in action


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 include the following:

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

CEE promotes the pooling and exchange of expertise, research findings, common platforms and processes, and empowers researchers and clinicians to rapidly exploit this trove of biological insights and clinical data for the benefit of patients

VHIO designed and leads the CCE-endorsed Basket of Baskets (BoB) trial.

BoB promises a more flexible and adaptive model in order to significantly accelerate patients’ access to an array of novel therapeutics. Its multi-modularity within the same trial, using common diagnostic and screening tools, will facilitate the assessment of alterations at the same time, as well as the efficacy of different agents, either as monotherapy or in combination. Several baskets/modules and different drugs will therefore co-exist with a single molecular screening, which will optimize patient stratification and enrolment.
www.cancercoreeurope.eu

As an important aside, independent of our CCE-endorsed BoB model, VHIO’s lead and participation in ‘designer’ trials including Basket, Octopus and first-in-human studies, is also exemplified by a selection featuring under From the Program Director, by Josep Tabernero.

Carried out in collaboration with VHIO’s Breast Cancer & Melanoma Group, directed by Cristina Saura, the SUMMIT basket trial showed how a single study can advance discovery into the biological dependencies in human cancers, and revealed that response to neratinib is driven by the characteristics of both tumor type and genomic variant.

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The EurOPDX Consortium – Translating Knowledge in Oncology, launched in 2013 to create a network of clinically relevant models of human cancer, patient-derived xenografts (PDXs) in particular. Connecting 18 cancer centers across 13 countries that are developing PDX cancer models, this initiative promotes the sharing and exchange of findings on promising therapeutics as well as leads multi-center preclinical studies. EuroPDX strives to reduce the duplication of efforts in oncology drug development and ultimately improve the quality of life and overall survival of cancer patients.

In 2018 Consortium members, along with additional European academia and SME partners secured funding from the European Union’s Horizon 2020 research and innovation programme to construct a repository for the open access sharing of over 1500 established PDX models complete with their clinical, molecular and pharmacological annotations.

This new platform, coordinated by colleagues at the University of Turin (Italy), with Principal Investigator Enzo Medico at the helm, is entitled EDIReX–EuroPDX Distributed Infrastructure for Research on patient-derived cancer Xenografts. Led by the EurOPDX Consortium and counting on the research excellence of 19 entities spanning 13 European countries, the resource will increase the predictability of preclinical data through the use of more reliable cancer models, extend the reach of EurOPDX, and further build on its outstanding achievements marked to-date.

The main aim of EDIReX is twofold. First, to facilitate data exchange among preclinical and translational cancer professionals working in academia as well as industry, and second, to promote, spur and consolidate scientific collaboration in PDX research across Europe.
www.europdx.eu

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

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

In 2018, results from the WINTHER trial; the first study promoted within the scope of WIN that was designed to navigate patients with advanced disease to therapy based on either next generation sequencing or transcriptomic analysis that compared tumor to normal tissue through its pioneering dual biopsy approach, were presented as an oral presentation during a Clinical Science Symposium at the American Society of Clinical Oncology’s (ASCO) Annual Meeting (01-05 June, Chicago, USA).

This talk, delivered by first author Jordi Rodón, Investigator at the MD Anderson Cancer Center (Texas, USA), also Associate Investigator of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Elena Garralda, showed that both genomic and transcriptomic analyses helped to more precisely guide therapy selection. Patients who received personalized treatments based on their genetic alterations independently associated with longer progression-free survival and overall survival.


In Memorandum

April 2018 marked the terrible loss of Thomas Tursz, a dedicated champion of WIN, eminent oncologist and recognized thought leader within our field.

As this Report entered into print, we were informed about the sad passing in January 2019 of John Mendelsohn, Chairman Emeritus of the WIN Consortium, also an internationally renowned leader in oncology.

Both were undisputed trailblazers who also spearhead many other ground breaking research programs, initiatives and cross-border collaborations. They will be sorely and deeply missed by us all.
www.winconsortium.org



Launched in 2018

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Led by Annette Byrne, Associate Professor, Royal College of Surgeons in Ireland (RSCI) Department of Physiology and Medical Physics, in partnership with leading clinical investigators and researchers spanning eight European countries, the Horizon 2020-supported COLOSSUS–Advancing a Precision Medicine Paradigm in metastatic Colorectal Cancer: Systems based patient stratification solutions, launched in early 2018 to more precisely define molecular subclasses of colorectal cancer (CRC).

By studying patient samples and applying cutting-edge, multi-omic modelling approaches, this Consortium is set to drive important progress towards developing, matching and measuring novel therapies according to the specificities of each identified molecular subtype.

Powered by 14 partners with expertise in cancer immunology, systems biology, computational modelling, bioinformatics, omics analysis, clinical oncology/pathology, preclinical research, medical imaging, clinical trials, health economics and patient management, this five-year research program focuses on microsatellite stable RAS mutant (MSS RAS mt) disease – a genetically identified type of CRC with very few therapeutic options available once patients develop resistance to existing chemotherapies.

The COLOSSUS team will strive to both expand and refine the classification of this particular subset of colorectal cancer.

Reflective of its promise to deliver multidisciplinary team science of excellence, the COLOSSUS proposal ranked first among the other 200 European projects that were submitted to the Horizon 2020 Personalized Medicine Call for New Concepts in Patient Stratification.
www.colossusproject.eu

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Led by Kathrin Thedieck, University Medical Center Groningen–UMCG (The Netherlands), and co-coordinated by Tobias Anzeneder from the German patient organization PATH Biobank, the MESI-STRAT Consortium combines the expertise of 14 partners, including VHIO, to establish the interplay of breast cancer metabolism and oncogenic signaling (Metabolic Signaling) by systems medicine approaches. Aimed at developing new models for knowledge-based stratification of patients into subgroups with different endocrine therapy resistance mechanisms, this pan-European undertaking, supported by the European Union’s Horizon 2020 research and innovation programme, represents an important forward step towards improving outcomes for these patients.

Spanning 6 countries, MESI-STRAT’s team is comprised of leading oncologists, modelers, bioinformaticians and experimentalists who will collectively pioneer breast cancer metabolism as a novel approach for the stratification of patients, tracking of resistance and better guiding clinical decision-making throughout the course of endocrine therapy.

Through the development of new computational models in combination with network analyses, pharmacogenomics and integrated multi-omics data, MESI-STRAT will play a decisive role in better deciphering the metabolic and signaling networks that drive resistance to endocrine-based therapies.
www.mesi-strat.eu

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Announced in November, one of the U.S. Department of Defense’s (DoD) Innovative Minds in Prostate Cancer (IMPaCT) Awards will fund a three-year collaborative partnership to advance precision medicine against metastatic prostate cancer (mPC). This coalition will count on the multidisciplinary expertise of investigators at VHIO, the Spanish National Cancer Research Centre–CNIO (Madrid, Spain), and the University of Washington (USA). Aimed at more precisely gauging response in patients to standard therapies, the team will also seek to develop new, more effective and tailored treatment strategies, as well as design a clinical trial to assess the performance of a DNA damaging platinum chemotherapy, carboplatin, that is already used to treat other tumor types including ovarian and breast cancer.

Research at VHIO led by Joaquin Mateo, Principal Investigator of our Prostate Cancer Translational Research Group, will search for DNA damage and repair biomarkers in these patients, since these deficiencies do not always originate from an inherited mutation.

His team will focus on biological parameters with clinical value by studying these tumors using a range of tools and techniques in the laboratory. The objective is to count on these new signals as indicators of damage – more so than genetic mutations – that will guide and accelerate more precise treatment decisions.
https://cdmrp.army.mil/pcrp

Accolades and achievements: a snapshot

We are delighted to report that 2018 has brought many important accolades and recognitions ‘at home’ and away. Here are just some of the many that made the headlines:

International recognitions

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VHIO’s Director, Josep Tabernero, and Enriqueta Felip, PI of our Thoracic Cancers & Head and Neck Cancer Group, were both named in the Global Highly Cited Researchers list 2018.

The Web of Science serves as the basis for the regular listings of researchers whose citation records rank them in the top 1% for their field and year. Their consistent production of highly cited papers reflects their essential contributions and utility of their work as repeatedly judged by their peers.

Featuring among the 4000+ top drawer leading researchers across 21 fields of the sciences and social sciences covered by the Essential Science Indicator (ESI), Josep was selected, for a consecutive year, for his exceptional advancements in cancer research under the category of Clinical Medicine that listed a total of 497 named leaders across the globe in 2018.

Devised to ‘house’ frontier areas of research that are frequently interdisciplinary, the newly launched cross-field category recognized some additional 2000 researchers who have been identified as having an exceptional performance based on high impact papers in several fields during the last decade. Among these multi-field contributors who have been selected in one or more of the 21 broad fields, was VHIO’s Enriqueta Felip.

Upon the eve of ASCO: Josep Tabernero, Director of VHIO and one of the 21 recipients of the OncLive Giants of Cancer Awards 2018. Left to right: Robert Goldsmith, OncLive, Josep Tabernero, Patrick Borgen, Chair of Giants of Cancer Care.

Now in their 6th Annual edition, the OncLive Giants of Cancer Care Awards recognize trailblazers in oncology for their remarkable achievements in advancing cancer research, clinical practice and patient care. The 2018 class of 21 Giants were nominated by the oncology community and finalists were selected by an especially appointed seven-member Advisory Board chaired by Patrick I. Borgen. Nominees were then voted on by a 100-plus member selection committee.

One of the 2018 Award recipients was our Director, Josep Tabernero. Specifically, under the category of gastrointestinal cancer, this recognition salutes Josep’s determined efforts aimed at advancing cancer research and precision treatment and care in oncology. Fittingly, the special ceremony took place on 31 May 2018 upon the eve of the Annual Meeting of the American Society of Clinical Oncology (ASCO) Annual Meeting, 01-05 June, in Chicago (IL, USA).


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2018 proved a particularly great year for VHIO’s Laura Soucek, PI of our Mouse Models of Cancer Therapies Group, ICREA Professor, and Co-Founder & CEO of VHIO spin-off, Peptomyc S.L. (www.peptomyc.com). This VHIO-born spin-off was established in 2014 and was co-created by Marie-Eve Beaulieu, CSO of the company and formerly a Postdoc in Laura’s group.

The European Research Council (ERC), among other ‘believers’ including its partners, venture capital firms Alta Life Sciences and HealthEquity, and ICREA, has consistently supported Laura and her group’s efforts in advancing discovery into Myc’s biology and function, and progressing novel targeting strategies towards finally delivering a clinically viable inhibitor.

In 2018 Laura was named as one among fifty other current ERC grant holders (totaling five from Spain, all located across Catalonia) to receive top-up funding via her Proof of Concept Grant (PoC), to explore the commercial and societal potential of the results of her ERC-funded frontier research, under EU’s research and innovation programme, Horizon 2020.

Laura Soucek, PI of our Mouse Models of Cancer Therapies Group.

Laura was the only woman in Catalonia to receive a ”la Caixa” EntrepreneurXXI Award in 2018. These annual recognitions, established by CaixaBank through Caixa Capital Risc in 2007, are co-granted by the Spanish Ministry of Economy, Industry and Competitiveness through ENISA – Empresa Nacional de Innovación, and support the development of innovative start-up companies throughout Spain and Portugal.

At the end of last year, on the occasion of the BioFIT meeting – Europe’s premier event for early-stage innovations in Life Sciences, Peptomyc was jointly awarded as the Most Innovative Life Sciences Start-up of 2018.


Raquel Perez-Lopez, PI of our Radiomics Group.

The Prostate Cancer Foundation (PCF), granted Raquel Perez-Lopez, who leads our Radiomics Group, with one of its 29 Young Investigator Awards 2018 for early career scientists with unique approaches and ground-breaking ideas to drive the critical research needed to more effectively combat prostate cancer.

More specifically, Raquel received the 2018 Gina Rinehart–PCF Young Investigator Award, to support her winning research proposal entitled: A Two-Stage study to Clinically Qualify Whole-Body Diffusion-Weighted MRI in Patients with Metastatic Castration Resistant Prostate Carcinoma with Bone Metastases.


Swiss Bridge Award Ceremony. Left to right: co-Award Recipient Ping-Chih Ho and his family, Jakob Passweg, President of Swiss Bridge, VHIO's Rodrigo A. Toledo, co-Award Recipient, Gordon McVie, President of the Award's Scientific Jury, and Philipp Lücke, the Foundation's CEO.

Celebrated during a special ceremony hosted and organized by the Swiss Bridge Foundation in Zurich, Switzerland, Rodrigo A. Toledo, Translational Investigator of VHIO’s Gastrointestinal and Endocrine Tumors Group, headed by Teresa Macarulla and directed by Josep Tabernero, was officially announced as joint recipient of the Foundation’s Annual Award in 2018.

Empowering exceptional cancer research across Europe, this year’s Call, inviting proposals from internationally-driven young research talents on the topic of immune-oncology biomarkers, received a total of 111 applications.

Recognized alongside his fellow winner, Ping-Chih Ho, Department of Fundamental Oncology at the University of Lausanne/Ludwig Lausanne Branch (Switzerland), Rodrigo A. Toledo’s project entitled, IMMUNOMICS: Co-evolutionary dynamics landscape of neoplastic cells and T-cells interactions during cancer immunotherapy, will be fueled by a half share of the 2018 Swiss Bridge Award funding.


At the ICS Award Ceremony from left to right: Josep Tabernero (VHIO’s Director), Elena Élez (ICS Awardee, VHIO), Miquel Casas (ICS Awardee, VHIR), Joan X. Comella (Director of VHIR), and Josep Antoni Ramos-Quiroga (Head of Psychiatry, Vall d'Hebron University Hospital).

At the regional and national levels

Celebrated during the 10th Research Workshop of the Catalan Institute of Health (ICS), Elena Élez, Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group, directed by Josep Tabernero and co-led by Principal Investigator Teresa Macarulla, was awarded the Young Investigator of the Year by ICS in recognition for her dedication to advancing precision research, treatment and care in colorectal cancer.

Created to both prize and promote biomedical, translational research of excellence led by researchers at entities belonging or affiliated to the ICS, this year’s recognition acknowledges the tremendous work of two up and coming young investigators. Both Elena and Beatriz Mothe, Investigator of the HIV Unit – Department of Infectious Diseases, the Germans Trias i Pujol University Hospital, were equally awarded.

In Elena’s case, this accolade not only recognizes her important contributions in biomarker development and rendering targeted therapies more precise, it applauds her essential collaboration in some 200 clinical studies spanning the early phases of clinical drug development, and congratulates her already renowned excellence as a tremendously devoted medical oncologist at the Vall d’Hebron University Hospital’s Medical Oncology Department (Vall d’Hebron Barcelona Hospital Campus), also spearhead by Josep Tabernero.

Celebrated at a gala event hosted by the National Royal Academy of Medicine in Madrid, the Fundación para la Excelencia y la Calidad en la Oncología (ECO) presented this year’s recipients with its annual awards. Now in its seventh edition, this accolade recognizes the outstanding contributions of individuals, bodies, societies and institutions to advancing the oncology field.

VHIO’s Director, Josep Tabernero (to the right), with ECO’s President, Vicente Guillem.

VHIO’s Director and Head of the Medical Oncology Department at the Vall d’Hebron University Hospital (HVUH–Vall d’Hebron Barcelona Hospital Campus), Josep Tabernero, was among the twenty awardees for 2018. To inaugurate the award ceremony, Josep was also invited to deliver the opening lecture on The Future of Oncology in Europe.

Importantly, ECO also recognized the tremendous successes marked to-date of the recently created Center for the Biomedical Research Network in Oncology (CIBERONC), which is expertly directed by Joaquín Arribas, Co-Director of VHIO’s Preclinical and Translational Research Program, and ICREA Professor. This virtual hub, incorporating and connecting fifty of the most renowned national research groups in cancer, promotes excellence in oncology throughout Spain and seeks to more swiftly and collectively translate new findings to clinical practice.

Timed to coincide with World Cancer Research Day (WCRD), celebrated each year on 24 September 2018, the Spanish Association against Cancer (AECC) announced its 2018 awardees during a special ceremony.

The 2018 AECC Awards Ceremony.

This essential support will fuel some 160 projects, two of which will be led by Ana Vivancos, Principal Investigator of Cancer Genomics at VHIO, and Marta Crespo, Translational Research Coordinator of our Experimental Hematology Group, who were awarded under the categories AECC Lab and AECC Project, respectively.

Ana will lead research on Moving liquid biopsy beyond current applications: the study of prognostic and predictive values of circulating tumor DNA in metastatic colorectal cancer, which she will carry out in collaboration with other VHIO teams and talents, including members of our Colorectal Taskforce.

Marta’s team will focus on Macrophage-mediated immunotherapy optimization in lymphomas affecting the central nervous system, to test their hypothesis that macrophages play a central role in the development of central nervous system lymphoma (CNSL) and its potential response to immunotherapies.

VHIO’s Director, Josep Tabernero, was also recognized as Co-Principal Investigator of one of the six international projects to have received an Accelerator Award from the newly established Cancer Research UK (CRUK), Associazione Italiana per la Ricerca sul Cancro (AIRC), and AECC charity partnership.

These highly competitive Accelerator Awards support international collaborations that promise to accelerate translational research against cancer. ACRCelerate: Colorectal Cancer Stratified Medicine Network, led by Owen Sansom, Director of the Cancer Research UK Beatson Institute in Glasgow, will count on VHIO’s expertise as one of its project partners. Incorporating a total of 20 international trailblazers in colorectal cancer, including Josep, this tour de force collaboration will seek to identify new therapeutic avenues for the treatment of this disease by discovering and validating novel targets so that patients can be more precisely matched to therapies under study.

Photo:GILEAD.

The 6th annual edition of Gilead’s Fellowships in Biomedical Research 2018 awarded VHIO’s Experimental Hematology Group for research on: Understanding the tumor immune microenvironment in diffuse large B-cell lymphoma for the development of immunotherapeutic strategies that target each individual’s immune biology, under the leadership of Principal Investigator of the project, Francesc Bosch (also PI of the same VHIO group).

Gilead Sciences Inc. actively supports and promotes Spanish research of excellence that focuses on advancing biomedicine and improving the quality of life of patients. Gilead’s funding spurs collaborations between public and private entities across the fields of HIV, Hepatitis and Hemato-oncology.

Evaluated and selected by the Institute of Health Carlos III (ISCIII), and organized in collaboration with the GeSIDA aids research group, the Spanish Association for the Study of the Liver (AEEH), and Spanish Association of Hematology & Hemotherapy (SEHH), 21 projects were awarded – eight of which were presented to researchers in Catalonia.

Specifically, Gilead will fuel their research focused on better understanding the role of the individual immune system in the treatment of diffuse large B-cell lymphoma (DLBCL), the most common type of adult and aggressive non-Hodgkin’s lymphoma, towards developing more effective therapies.

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Recognition through accreditation

The European Commission’s Human Resources for Research (HRS4R) strategy enables research institutions of excellence to actively implement and uphold the requisites of The European Charter for Researchers and Code of Conduct for the Recruitment of Researchers for their HR policies and practices.

VHIO’s comprehensive analysis and action plan was officially approved by HRS4R assessors in 2018 and our Institute was consequently granted permission to use the HR Excellence in Research Award logo as demonstration of its stimulating and favorable work environment.

Importantly, it’s not just a matter of the working environment. VHIO is dedicated to providing a bias-free environment that stimulates our faculty to follow their research ambitions, develop their careers and seize on the same, equal opportunities.

Throughout 2018, several editorials and opinion pieces published in leading specialized media rightly called for targeted action against gender gaps and the need to advance equity in science, medicine and global health.

To name but two, our Director was invited to pen an editorial in ESMO Open exploring the current status of women in oncology, particularly in terms of fair access to more senior roles (1). As this Scientific Report entered into print, a piece in The Lancet (2) argued that achieving gender balance is a shared responsibility of everyone and is not just about equal rights; it is imperative in producing the very best research and providing optimal patient care.

We are proud to report that 74% of VHIO’s workforce are women, and over half of our Principal Investigators are female.

1. Tabernero J. All change: closing the gender gap in oncology. ESMO Open. 2018 Nov 15;3(7):e000448.
2. Feminism is for everybody. Lancet. 2019 Feb 9;393(10171):493.


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.


Ad-hoc courses, workshops & observerships

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

Exchanging latest discovery in cancer science and medicine, VHIO organized and hosted a total of 50 Courses, Workshops, Observerships and Perceptorships in 2018.

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1. Towards New Horizons in Metastatic Colorectal Cancer, 19 April 2018, Course Directors: Elena Élez and Jaume Capdevila. 2. Medical Education Program on Immunotherapy, 17-18 May 2018, Program Director: Elena Garralda. 3. Highlights in Chronic Lymphocytic Leukemia Dates: 05-06 July 2018, Course Director: Francesc Bosch.

Co-organized and hosted by VHIO: EACR’s LIF As We Know IT

An EACR Masterclass celebrated at VHIO’s CELLEX CENTER: LIF as We Know It – from Basic Science to Clinical Trials, 28-29 May, 2018.

Scientifically co-organized by Joan Seoane, Co-Director of Preclinical and Translational Research at VHIO, ICREA Professor, Secretary General of the European Association for Cancer Research (EACR) and Chairman of its Conference Series Committee, VHIO opened the doors of its Auditorium to welcome speakers and participants of EACR’s two-day meeting on LIF As WE Know It: from Basic Science to Clinical Trials.

This inspired meeting was superbly engineered to offer a broad, stimulating and comprehensive overview of the most recent advances in the LIF field from the preclinical, translational and clinical perspectives. Testament to the caliber of this event, a post-conference survey achieved a 100% recommendation rate and ranking of scientific quality as ‘excellent’ or ‘very good’.


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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.

Benchstorming co-Chairs, Elena Senís and Toni Jauset.

As the Benchstormings turned two years old, Verónica and Jordi handed over to new Co-Chairs in March 2018, Elena Senís, Post-Doctoral Fellow of VHIO’s Cellular Plasticity & Cancer Group, and Toni Jauset, formerly a graduate student of VHIO’s Mouse Models of Cancer Therapies Group and now researcher at VHIO-born spin-off Peptomyc S.L.

In 2018, a total of 20 researchers discussed and ‘benchstormed’ their research areas. Elena and Toni also introduced an additional element to this popularly attended program: the ‘spin-off’ Techstorming sessions to present on novel technologies and latest lab approaches in cancer research.


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 2018, VHIO led and/or participated in over 30 public outreach events, programs and initiatives spurred through the dedication of the following entities, events as well as fundraising efforts (listed in alphabetical order):

  • II Jornadas Baby Beatles
  • 48H Open House BCN
  • Al cáncer, donem-li recerca!
  • Asociación Cáncer de Mama Metastásico’s visit to VHIO
  • BCNspiracy
  • Concierto “Jarabe y amigos contra el cáncer”, Pau Donés
  • El Corte Inglés se viste de rosa
  • Festival de la Ciencia
  • Healthio 2018
  • Marató de TV3 i Cataluna Ràdio
  • Pink Run Mir
  • Projecte Mexcla’t
  • The Youth Mobile Festival: YoMo
  • VHIO’s Escuela y Ciencia program
  • VHIO-HUVH’s annual series of workshops for patients suffering from breast cancer
  • VHIO-IDIBELL-ICO workshops on prostate cancer
  • VHIO’s Running for Research (R4R)
  • Zumba solidario

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

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

Just two of the many runathons in which R4R participated in 2018 included the Barcelona half marathon for a FERO Foundation crowdfunding in support of research at VHIO, and the Spanish Association against Cancer’s (AECC), Run against Cancer.

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VHIO’s R4R rallying for research against cancer: 1. At the Barcelona half marathon for FERO Foundation’s inspired crowdfunding. 2. Participating at the Spanish Association against Cancer’s (AECC) Run against Cancer.

Concerning the former, they teamed up with FERO Foundation participants for their crowdfunding initiative to help fuel the continued development of liquid biopsy technology at VHIO. At AECC’s second annual Barcelona-based fundraising run, R4R joined other runners to help rally for research in the 10K race, 5K run, and the gentler paced 2.5K.


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In 2018 VHIO’s education program, Schools and Science, welcomed a total of over 250 under-twelves from 6 local primary schools to meet our faculty, tour our laboratories and learn more about cancer biology and research.

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Junior masterclasses and hands-on workshops to explain 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 visits 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 program, with dates already in the diary for next 2019.

In 2018 we celebrated the launch of a new institutional public engagement program: VHIO-IDIBELL-ICO’s workshop series focused on prostate cancer.

Pioneered by the patient advocacy group, The Prostate Net, these informal meetings aimed at patients, their families, and the public at large, are co-organized by Joaquin Mateo (PI of our Prostate Cancer Translational Group), and Álavaro Aytes (PI of the Resistance and Progression Mechanisms in Prostate Cancer Group, Bellvitge Biomedical Research Institute, Barcelona), and aim at increasing awareness on and around the importance of cancer science and clinical discovery in advancing treatments against this tumor type, as well as update on the latest developments within the field.

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Co-organizers Joaquin Mateo and Álvaro Aytes at the inaugural morning workshop, pioneered by Virgil H. Simons, Founder and President of The Prostate Net, that took place at the Harley Davidson 99%, Barcelona.

These workshops are conducted in Castilian and Catalan and the inaugural, entitled, Fighting Prostate Cancer: From the Laboratory to the Patient, 23 November, explored the bench-to-bedside (and back) steps and stages that drive the advancement and delivery of more effective anti-prostate cancer therapies.


Continued evolution: VHIO's international and internal scientific communication

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 translational research lines, programs and projects.

Its sub-portals in Castilian and Catalan, generally aimed at less specialized, lay audiences, publish our media releases in these two languages, as well as update on our local public outreach activities.

VHIO’s International Communications, directed by Amanda Wren, continues to upgrade and constantly update our website’s content, adding exciting programs as they launch, and implementing new features aimed at further generating traffic, maintaining and attracting new visitors.

Just some of the many additions in 2018 included the incorporation of VHIO’s Twitter account @VHIO which we launched just as this Scientific Report entered into print (end January 2019), as well as our new corporate video:

Kicking-off with the question, How can you translate basic discovery into more precise and potent anticancer therapies?, our newly launched video responds by telling VHIO’s story.

It does so by dipping into our Institute’s history, presenting a snapshot of our main programs and activities, and signposting a promising future ahead.

The film’s title? Simply, VHIO’s tagline: Translation toward precision oncology.

To discover more about our purely translational and multidisciplinary research model and just how we bridge preclinical and clinical research, we invite you to access our video here:

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Celebrating its first birthday in December 2018, 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. Reflective of its popularity and keen VHIO following, Wren’s Lens has since become more of an internal blog spot than a ‘news desk’ update.