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96 Pages·2015·5.41 MB·English

2014
SCIENTIFIC REPORT
VALL D’HEBRON
INSTITUTE
OF ONCOLOGY
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INDEX
SCIENTIFIC REPORT
more info at www.vhio.net
Vall d’Hebron Institute of Oncology (VHIO)
Passeig Vall d’Hebron 119
Edifici Maternoinfantil, planta 14
08035 Barcelona, Spain
Tel: [phone]
email:
52 High Risk & Cancer Prevention Group
INTRODUCING VHIO
54 Oncogenetics Group
04 Foreword 56 Radiation Oncology Group
58 Thoracic Tumors Group
08 VHIO in 2014: the transformative power of forward-thinking talent
14 Scientific Productivity: research articles
15 Selection of some of the most relevant articles by VHIO researchers
published in 2014 CORE TECHNOLOGIES
The PI Pages
62 Cancer Genomics Group
PRECLINICAL RESEARCH
64 Molecular Oncology Group
21 From the Director 66 Proteomics Group
The PI Pages 68 Translational Genomics Group
22 Experimental Therapeutics Group
24 Growth Factors Group
26 Mouse Models of Cancer Therapies Group VHIO TRANSVERSAL CLINICAL TRIALS
28 Tumor Biomarkers Group
CORE SERVICES & UNITS
72 Clinical Trials Office
TRANSLATIONAL RESEARCH 76 Research Unit for Molecular
Therapy of Cancer (UITM) - ”la Caixa”
33 From the Director
78 Clinical Research Oncology Nurses
The PI Pages
80 Clinical Research Pharmacy Unit
34 Gene Expression & Cancer Group
36 Stem Cells & Cancer Group
83 Full listing of articles published
CLINICAL RESEARCH by VHIO Investigators in 2014
41 From the Director
The PI Pages
42 Breast Cancer & Melanoma Group
44 Early Clinical Drug Development Group 92 Funding & Consortia
46 Gastrointestinal & Endocrine Tumors Group
48 Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary
Site Group
50 Head and Neck & Gynecological Tumors Group
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Foreword
As I reflect on the past year, not only considering the Although mortality from cancer is on the decrease in Europe,
many positive advances reported by VHIO’s outstanding thanks to our increased understanding of the hallmarks of
and committed multidisciplinary teams but also major cancer, earlier diagnosis, and more powerful anti-cancer
achievements of our colleagues from comprehensive cancer therapeutics, incidence is on the rise. In a recent paper
centers of excellence around the globe, I am pleased to report published in the British Journal of Cancer, colleagues from
that yes, we are collectively progressing in rendering precision Cancer Research UK (CRUK) forecast that one in two people
medicine in oncology a reality for an increasing number of will develop cancer at some point in their lives. The one in three
patients. has now alarmingly increased to two. This, coupled with an
ever-increasing ageing population, translates into a daunting
There are many factors that have led us to this turning point prospect over the next decades. We must therefore combine
in the delivery of more precise and powerful anti-cancer forces, working more closely with all oncology professions and
therapies. Important advancements in defining the molecular stakeholders to ensure faster, streamlined results, a quicker
basis of cancer, for example, have enabled us to leverage those development and implementation of targeted, more affordable
insights in the selection of rational, targeted therapies. treatment plans for an increasing number of our patients.
Josep Tabernero
Director
The Vall d’Hebron Institute We can most certainly afford to be optimistic, but, with At the close of 2014, hot debate was sparked by a paper
of Oncology (VHIO) caution. I was recently asked to respond to the question: published in Science authored by Bert Vogelstein and
Will all cancer patients be treated by targeted therapies in the colleagues at Johns Hopkins University School of Medicine.
next ten years? On the one hand, while translational research The study made headlines around the world as the Hopkins
efforts are driving cancer discovery at a rapid pace, cutting- team concluded that a large proportion of cancer cases was
edge technologies are becoming yet more powerful and attributed to “bad luck.” Whatever conclusion you may draw,
indeed precise, and the lower costs associated with genomic the major risk drivers of cancer are known. Adding to the mix is
sequencing and pre-screening platforms are making precision the so-called exposome -- environmental exposures that may
medicine more accessible to more of our patients. But we still contribute to increased probability of disease. This aspect
have a long road to travel. Regretfully, in view of the present of cancer research warrants much more attention even as
scenario, my answer to that question had to be no. we celebrate successes in the genomic profiling of patients’
tumors.
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Throughout 2014, VHIO has continued to up the tempo Importantly, VHIO’s pre-screening program currently and dodge potent anti-cancer therapeutics. The need to
in its basic, translational and clinical research efforts by analyses the tumors of some 1000 patients per year better monitor and predict its every move is critical if we
reinforcing current infrastructures, increasing its portfolio -- those individuals who have exhausted all other are to improve outcomes for our patients and deliver on
of technologies and clinical trials, as well as building upon standard therapies and are in critical need of alternative the promise of precision medicine.
cross-border partnerships. We have one collective goal treatment regimens. If we are to extend these efforts
in mind: to get the right treatment, to the right patient, at to an increasing number of patients, we will need to In this emerging era of personalized medicine in cancer,
the right dose, at the right time. We are better equipping do so in collaboration. In this respect, I am proud to research breakthroughs have now rendered biopsies
our teams to more precisely tackle the specificities of announce the VHIO-Catalan Institute of Oncology more precise in detecting cancer mutations, tracking
each individual cancer, across all tumor types, and thus (ICO) Research Alliance. Representing the biggest the evolution of disease and circulating tumor cells
respond to the many challenges and yet unanswered clinical cancer care provider in Catalonia, this powerful that drive metastasis, as well as predicting response
questions that still remain in our battle against cancer. collaboration incorporates four comprehensive to therapy. There is enormous excitement about liquid
cancer centers throughout the region, providing biopsies -- blood tests that can non-invasively reveal
clinical care to some 16,000 patients on a yearly circulating tumor DNA that is released by tumor cells
VHIO’s cutting-edge technologies, tests, and basis. Direct access to extended patient populations into the bloodstream. This circulating DNA contains vital
platforms: powerful armory against cancer will undoubtedly provide essential insights to more signals, components and genetic information about
rapidly translate research into more effective, targeted what is actually occurring in the tumor, providing us with
treatments and better practice for the future care of a much bigger picture regarding the specificities and
Thanks to the dedicated work of our Cancer Genomics
our deserving patients. status of the patient’s cancer.
Group headed by Ana Vivancos, our pre-screening
efforts for mutations in patients who are candidates for
enrollment in our broad portfolio of Phase I clinical trials VHIO’s suite of cutting-edge technologies and assays Of tremendous importance in improving detection and
carried out at the Research Unit for Molecular Therapy including the nCounter Nanostring and RNAseq following cancer’s every move, is that these blood-based
of Cancer (UITM) - ”la Caixa”, led by Jordi Rodón’s Early platforms, coupled with the expertise of our Core biopsies also allow for serial samples in order to identify
Clinical Drug Development Group -- have established Technology teams who both develop and implement tumor genomic alterations not only in real time, but over
VHIO as one of the few groups in Europe to run such these techniques, enable us to bring more detailed time.
prognostics directly to the clinical setting, and further
a comprehensive program. Using a custom amplicon
develop and validate the next generation of tests. 2014
panel, VHIO-Card, we study mutations in 61 oncogenes As this Scientific Report goes to print, as part of a
marked the successful implementation of a clinically
and tumor supressors at the same time, across all collaboration with Merck Serono and Sysmex Inostics,
applicable gene expression based test, known as PAM
tumor types. Ana’s team screens for both known we have just announced that VHIO will be the first
50, for the management of breast cancer patients.
mutations as well as those for which there are novel academic test center of its kind to use in-house
Significantly, our Translational Genomics Group led
targeted therapies in the drug development pipeline. BEAMing liquid biopsy RAS biomarker technology.
by Aleix Prat was the first to do so in Europe. Such
By broadening the scope of mutations under study we Initially we will use blood-based technology to evaluate
pioneering efforts will continue to empower VHIO in
unmask more mutated samples, thus opening up more patients with metastatic colorectal cancer at research
significantly contributing to better-guided treatment
possibilities for patient stratification. level. Expected to receive its European Conformity
decisions as well as improved outcomes for patients.
approval (CE mark) in 2015, this RAS biomarker test
Deciphering the molecular profile of each patient promises a more precise treatment for metastatic
indicates his/her suitability for inclusion in a given colorectal cancer patients.
clinical trial aimed at testing the usefulness of novel Liquid biopsy ‘policing’ of cancer:
targeted therapies, such as PI3K, AKT, BRAF or MEK ready for prime time? I see enormous potential for liquid biopsies, so much so
inhibitors. These endeavors are not only revolutionizing that I think they could, in the near future, replace tumor-
tumor classification but also increasingly impacting on One of the main challenges of cancer is its complex section analysis and expand the scope of personalized
how cancer treatment decisions are made. genetic landscape coupled with its ability to outsmart medicine for our patients. In short, the liquid biopsy
more info at www.vhio.net VHIO Scientific Report 2014 5
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undoubtedly represents a potent new contender in our of biological insights and clinical data for the benefit of cross-talk necessary to carry out multidisciplinary and
current weaponry against cancer. patients. translational research and medical practice -- as is
evidenced by the updates described by each group in
I also want to highlight the successes to date of the this Scientific Report.
Synergies and the same score sheet: SPECTAcolor - Screening Platform for Efficient Clinical
empowerment through collaboration Trials Access in Colorectal Cancer. Set up in September VHIO’s leading scientists and physician-researchers are
2013 and funded by a corporate social responsibility tirelessly advancing their research, and, as a reflection
While our preclinical, translational and clinical research program of Alliance Boots, SPECTAcolor is an initiative of excellence, continue to secure precious funding that
efforts are certainly translating into benefits for patients, set within the framework of the research program of fuels their efforts in combating cancer. As I noted in last
we must continue to share our expertise -- and benefit the EORTC and is a unique undertaking as the first year’s Foreword, Horizon 2020 replaced the European
from the knowledge of others -- through cross-border ever prospective, fully annotated tumor biobank and Union Framework Programmes with the emphasis on
collaboration (see pages 94 - 95 for VHIO’s participation biomarker analysis platform for the genetic profiling of frontier and interdisciplinary research with one of the
in various Consortia of international excellence). Such patients suffering from advanced colorectal cancer. topics favoring novel studies and clinical approaches
global exchange of data and ideas is crucial not only supporting the optimization of available therapies,
in accelerating advances but also to avoid wasteful Implemented across 19 clinical centers located in specifically drug repurposing. Since talent fosters
duplication of efforts. nine countries throughout Europe, including VHIO, it opportunity, we are optimistic that our proposals will be
has succeeded in recruiting over 500 patients. This suitably considered and ultimately rewarded through
promising start has demonstrated its viability to this European funding.
Launched at a special press conference during the
facilitate next-generation cancer clinical trials and that
2014 Congress of the European Society for Medical
Oncology (ESMO) last Autumn, Cancer Core Europe a logistically complex infrastructure in a multinational I would also like to personally thank our devoted
is a unique partnership aimed at addressing the setting is achievable -- proving that where there is willing, institutional supporters, the Generalitat de Catalunya,
cancer care-cancer research continuum. This working there is certainly a way. FERO, the Fundació Bancària “la Caixa”, the Fundación
consortium represents a critical mass of activity for the BBVA, with the invaluable support from the Fundació
successful integration of all cancer care information, As dedicated partner, VHIO will continue to accrue Privada Cellex, as well as VHIO’s many other supporters,
clinical research and outcome research, spearhead patients at local level through the Vall d’Hebron funding entities and agencies (see pages 92 - 93 of this
by the six founding partners and leading European University Hospital’s Medical Oncology Department, as report).
comprehensive cancer centers: the Gustave Roussy well as advance biomarker discovery aimed at the rapid
Cancer Campus Grand Paris (Villejuif, France), development of novel therapies targeted to the needs of VHIO will only deliver on its goal of accelerating the
Cambridge Cancer Centre (Cambridge, UK), Karolinska each individual colorectal cancer patient. pace in advancing personalized and targeted therapies
Institute (Stockholm, Sweden), Netherlands Cancer against cancer thanks to the public funding it receives,
Institute - NKI (Amsterdam, The Netherlands), National as well as through such generous support from private
“We are told that talent creates its own
Center for Tumor Diseases - DKFZ-NCT (Heidelberg, institutions, companies and individuals, all of whom
opportunities. But it sometimes seems
Germany), and VHIO. share the intense desire and drive to ensure the clock
that intense desire creates not only its own
continue to tick in our favor - against cancer. This
opportunities, but its own talents”
This consortium marks a significant forward step in collective ambition not only allows us to do what we at
harnessing, storing and sharing an overwhelming wealth - Eric Hoffer, American social writer and VHIO do best -- rapidly translate cancer discovery into
of data generated through the ’onco’omics, clinical trials, philosopher (1902-1983). real benefit at clinical level -- but it also fosters essential
cancer science and medicine. The Cancer Core Europe’s growth and expansion of our programs.
pooling and exchange of expertise, research findings, As Director of VHIO, I am extremely proud of our
common platforms and processes, will empower talented teams of excellence who work together across In this respect, I am delighted to confirm that we have now
researchers and clinicians to rapidly exploit this trove programs in order to ensure the tight connectivity and successfully recruited new talent and groups in areas
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including cancer immunology and immunotherapy that translational trajectory. Providing the valuable space
will join us in 2015 to lead novel research focused on areas through which to grow, the new building will bring all our
such as the tumor microenvironment, immuno-oncology, multidisciplinary teams together under the same roof to
and the development of immune-based personalized enhance collaboration and spur our dedicated efforts to
therapeutics. To flank our efforts aimed at integrating combat cancer.
clinical translational research with genomics for precision
cancer therapy, I am delighted that Rodrigo Dienstmann At VHIO, as we demonstrate year after year, we have the
will be returning to VHIO from Sage Bionetworks, Fred desire, the talent and the opportunity to raise the bar and
Hutchinson Cancer Research Center, USA, to set up and set our ambitions even higher.
lead VHIO’s Oncology Data Science Group.
Josep Tabernero
Mention of expansion cannot be made without updating Director
on the status of our new home -- the CELLEX building. We The Vall d’Hebron Institute
are now ready to move in -- marking a new era in VHIO’s of Oncology (VHIO)
more info at www.vhio.net VHIO Scientific Report 2014 7
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VHIO in 2014: the transformative power of forward-thinking talent
WHO WE ARE AND WHAT WE DO
VHIO’s Organigram 2014 the fundamental biology of human cancer, from cellular and molecular biology and
genetics through to therapeutics.
In order to translate cancer discovery into real benefit for an increasing number
patients, VHIO has, from the very outset, adopted a purely translational, Its optimal organizational structure allows VHIO talents to continue to both anticipate
multidisciplinary research model. Organized into four main programs – Preclinical, and tackle the many unresolved questions in ultimately outsmarting the multifaceted,
Translational, Clinical, and Core Technologies, our research focuses on understanding heterogeneous and complex disease that is cancer:
BOARD OF TRUSTEES
SCIENTIFIC ADVISORY BOARD
EXECUTIVE COMMITTEE
DIRECTOR SCIENTIFIC COMMITTEE
Josep Tabernero President: José Baselga
MANAGING DIRECTOR Ext. Relations
Andrés de Kelety
Eco. & Finances
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Research Support Office
Growth Factors Gene Expression Cancer Transversal Clinical Research Cancer Genomics
Experimental Stem Cells & Cancer Services/Units Groups Proteomics
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Mouse Models of Cancer (UITM) - Development Scientific Equipment Unit
of Cancer Therapies ”la Caixa” Gastrointestinal &
Research Nurses Endocrine Tumors
Clinical Trial Genitourinary, CNS
Pharmacists & Sarcoma Tumors
Databases Head and Neck &
& Statistics Gynecologic Cancer
High Risk & Cancer
Current Research Structure Prevention
Managing Structure Thoracic Tumors
Scientific Advisory Board Nominated by the Patronage
Oncogenetics
Management Committee
(*) Coordinated Group Radiotherapy*
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A LITTLE EXTRA ON HOW WE DID IT IN 2014
Aside from the many highlights described by each of our groups in this report, we would like to underline a few
other important factors and developments in 2014 that enabled us to further advance cancer discovery through
the integration of translational science and clinical research within a multidisciplinary setting - - the winning formula
behind what we do and how we do it at VHIO:
VHIO’s translation towards precision oncology sequencing panels of genes or entire genomes in cancer
patients, we are now better equipped than ever before
Established in 2006, VHIO is a leading comprehensive
to identify specifi c molecular risk factors and gauge
cancer center of excellence where its scientists and
the potential effi cacy of specifi c agents for individual
research physicians adopt a purely translational research
patients. In parallel, these technologies (Hiseq2500,
model, working together as multidisciplinary teams to
MiSeq, nCounter Nanostring), accelerate our research
both accelerate and advance personalized and targeted
eff orts of our preclinical, translational and clinical
therapies against cancer.
scientists, enabling the identifi cation of mechanisms
of resistance to targeted therapies, the study of clonal
Undertaking one of Spain’s most dynamic cancer
populations, as well as defi ning novel therapeutic
research programs, VHIO is dedicated to delivering on
opportunities based on mutation profi les.
the promise of ’precision’medicine in oncology – turning
cancer discovery into more eff ective treatments and
Our Cancer Genomics Group (see pages 62 - 63) leads
better practice for the care of our patients.
VHIO’s pre-screening program of mutations in patients
who are candidates for our portfolio of Phase I clinical
trials. Assessing the molecular make-up of each patient
Oncogenomics and pre-screening
provide us with vital insights regarding the suitability for
At the core of VHIO’s research activities lies our suite of enrollment in clinical studies aimed at testing the effi cacy
cutting-edge core technology platforms which allow our of novel anti-cancer therapeutics. Our pre-screening
expert teams to apply next-generation whole-genome eff orts have already established VHIO as one of the few
sequencing for precision oncology as well as develop and centers in Europe to run such a comprehensive program.
improve existing applications to drive faster results. By We will be looking to expand our eff orts to an increasing
more info at www.vhio.net VHIO Scientifi c Report 2014 9
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number of patients thanks to the VHIO - Catalan Institute Clinical trials at VHIO: driving drug development In December 2014, in recognition of the support we
and targeted therapies against cancer
of Oncology (ICO) Research Alliance, representing the receive from the Fundació Bancària “la Caixa” and
biggest clinical care provider in Catalonia – see page 5 the tremendous successes marked since the UITM
of the Foreword to this report for more details. was inaugurated in 2010, we hosted and celebrated a
joint press conference. Attended by some 20 leading
As also detailed in our Director’s Foreword, VHIO, in journalists throughout Spain, the conference also
collaboration with Merck Serono and Sysmex Inostics, counted on the participation of two of our wonderful
will be the fi rst academic test center of its kind to patients who related their respective patient journeys
use in-house BEAMing liquid biopsy RAS biomarker as well as addressed the many questions put directly to
technology. This technology will initially be employed them by the media.
to evaluate metastatic colorectal cancer patients at
research level. Once it receives its European Conformity
approval, envisaged in 2015, this technology will be
extended to conventional routine care and to addtional
tumor types.
VHIO has increasingly established itself as a leading
reference in drug discovery from concept to the clinic.
It has been able to do so not only through the bridging
and tight connectivity between health care professionals,
VHIO scientists and physician researchers but also
through its Research Unit for Molecular Therapies of
Cancer (UITM) “la Caixa” (see pages 76 - 77) located
in the patient care environment of the Vall d’Hebron
University Hospital (see next page), and set within the
research context, as well as the Clinical Trials Offi ce of
the same hospital (see pages 72 - 75).
BEAMing digital PCR/fl ow cytometry technology: set to empower VHIO’s existing
suite of cutting-edge technologies.
Research at the UITM is led by VHIO’s Early Clinical Drug
By bringing more detailed prognostics directly to the Development Group (pages 44 - 45), focusing on both
clinical setting, and further developing and validating the development of new drugs based on the molecular
the next generation of tests, VHIO will signifi cantly profi le of each tumor as well as the optimization of
contribute to better guided treatment decisions as well treatment regimens using combinations of new drugs
as improved outcomes for patients, real time -- over with existing ones. In 2014, 83 Phase I clinical trials
time. were performed at the Unit, with a total of 303 patients
enrolled. The Clinical Trials Offi ce coordinates a large
portfolio of Phase I – II – III studies and consistently
reports an increase in the number of trials conducted
each year. In 2014 the number of patients included in our
studies totaled at 771 across 246 trials.
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