A European Platform for Translational Cancer Research
In response to these challenges and in line with the call, EurocanPlatform will work towards the goal of decreasing cancer mortality by dealing with three main areas of strategic research: prevention, early detection and improved treatments. It will build the necessary resources and know-how for the entire research continuum: basic research, early and late translational research, clinical research, epidemiological research, implementation in care and population based outcome research. There will be a strong focus on discovery-driven translational cancer research in five selected tumours: breast, head-neck, lung, malignant melanoma and pancreatic cancer. Joint structures and programmes for early detection will contribute to optimal treatment, and novel prevention research programmes will integrate prevention activities in clinical cancer centres as well as public prevention. Collaborations will also include molecular pathway-driven clinical research supported by joint structures for omics, biobanking and biomarker validation to support clinical trials aimed at enhancing patient benefits by individualised treatments.
EurocanPlatform is unique in its nature and represents a commitment from cancer centres to join forces and resources in order to fight cancer.
Nobels Vag 5
Higher or Secondary Education Establishments
€ 1 708 115
Maria Von Witting (Ms.)
Sort by EU Contribution
€ 541 022
€ 625 688
OSLO UNIVERSITETSSYKEHUS HF
€ 647 900
FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
€ 197 700
FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI
€ 560 300
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
€ 787 705
INSTITUT GUSTAVE ROUSSY
€ 479 200
CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER
€ 725 100
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
€ 135 600
ISTITUTO EUROPEO DI ONCOLOGIA SRL
€ 144 800
THE CHRISTIE NHS FOUNDATION TRUST
€ 105 600
Orszagos Onkologiai Intezet
€ 84 525
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
€ 1 869 613
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
€ 310 200
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
€ 766 700
INSTITUT JULES BORDET
€ 51 600
EUROPEAN MOLECULAR BIOLOGY LABORATORY
€ 964 456
THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL
€ 225 600
ACADEMISCH ZIEKENHUIS LEIDEN
€ 69 600
Fundación Instituto Valenciano de Oncología
€ 34 200
"INSTITUTO TUMORI ""GIOVANNI PAOLO II"""
€ 66 710
FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON
€ 260 333
€ 307 997
European CanCer Organisation
€ 50 590
GROUPEMENT EUROPEEN D INTERET ECONOMIQUE ORGANISATION OF EUROPEAN CANCER INSTITUTES OECI
€ 122 200
EUROPEAN CANCER PATIENT COALITION
€ 73 800
EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER AISBL
€ 81 600
Grant agreement ID: 260791
1 January 2011
31 December 2016
€ 15 561 005,72
€ 11 998 454
Europe unites against cancer
Grant agreement ID: 260791
1 January 2011
31 December 2016
€ 15 561 005,72
€ 11 998 454
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Final Report Summary - EUROCANPLATFORM (A European Platform for Translational Cancer Research)
The EurocanPlatform brought together 28 European cancer Institutions and organisations to work in partnership to structure translational research. The centres shared infrastructures, expertise and collaborated on projects to innovate in cancer research. The overarching aim of the project was to improve outcomes for cancer patients and reduce mortality. To achieve this, the partners worked on strategies focusing on key areas of research: prevention, early detection, therapeutics, and outcomes research. The EurocanPlatform covered the whole cancer continuum from bench to bedside: basic research, early and late translational research, implementation in care, and population-based outcome research. Significant achievements during the six years include:
Therapeutics: The establishment of Cancer Core Europe has been one of the main outcomes of the EurocanPlatform. The consortium, which comprises six large European cancer centres, has a significant critical mass; per year it sees 60,000 newly diagnosed patients, treats about 300,000 patients, has about 1,200,000 consultations, and around 1,500 clinical trials are being conducted. Six task forces have been established (data sharing, molecular diagnostics, immuno-oncology, imaging, clinical trials, and training and education) to share best practices and harmonize protocols, and strong links with the pharma industry have been established. Cancer Core Europe has provided an inspiring example of how to build research communities where all the strategic priorities set by Commissioner Carlos Moedas (3 O’s) could develop and progress in accord to tackle a major societal challenge such as cancer. Cancer Core Europe is expected to function as an infrastructure to stimulate collaboration with industry and global collaboration in a multi-stakeholder setting, and represents a first step towards the creation of a virtual European Cancer Institute.
The breast cancer trial Poseidon has entered Phase II and will be completed during 2017. UCAM, NKI and VHIO collaborate with Genentech in this trial.
Prevention: Encouraged by the activities leading to the creation of Cancer Core Europe, C. Wild from the IARC initiated similar efforts to create Cancer Prevention Europe. The initiative aims at establishing a sustainable structure for cancer prevention, and currently, there is a draft consortium agreement in place in which six centres have committed to a long-term collaboration.
Early detection: Detection of premalignant lesions, as well as invasive and metastatic disease, have been explored via biomarker discovery. Early tumours, premalignant lesions and liquid biopsies have been analysed yielding several significant achievements. Early detection plays an important role both for therapy and prevention activities and the construction will feed into both consortia.
Outcomes research: Strategies for clinical validation have been outlined. The network created during the EurocanPlatform project will continue to collaborate on selected pilot projects. Outcomes research will be of fundamental importance both for therapeutics and prevention research in the context of Cancer Core Europe and Cancer Prevention Europe.
Integration of preclinical and clinical cancer research (animal models, biomarker discovery): Long-term early translational research collaboration has been established supporting both prevention and therapeutic research.
Designation methodology for Comprehensive Cancer Centers (CCCs) of Excellence: The EurocanPlatform in collaboration with the European Academy of Cancer Sciences (EACS) established a designation methodology for CCCs of excellence aimed at assessing translational cancer research. The methodology, which was piloted under the platform, is now ready to use with the EACS as the designation body. The designation will be used to evaluate centres for inclusion in Cancer Core Europe.
Training and Education: The Summer School in Translational Cancer Research has been performed four times since 2011, and has been instrumental to train and network young researches/clinicians. Cancer Core Europe has agreed to take over the organisation of the School with the support of German Cancer Research Consortium. A program for the education of the next generation of leaders within CCE is another sustainable deliverable from the EurocanPlatform project.
Project Context and Objectives:
Cancer: a major societal problem
Cancer is one of the major health issues affecting our society and predicted to grow significantly globally as the population ages. In the forty countries of Europe, cancer diseases are expected to increase from 3.6 million cases in 2015 to 4.3 million cases in 2035, i.e. an increase of around 20%, which translates to 716,000 additional cases each year. While cancer is already considered as a major chronic disease, the number of patients living with cancer is predicted to escalate from 28 to 82 million globally for the same timeline. Trends are similar in Europe, where in 2006 cancer caused 1.7 million deaths, an equivalent of three deaths/minute.
This will cause the health care system to suffer a substantial extra demand, including required surveillance and recurrent treatment of both the disease and observed complications. Europe has no clear strategy to meet the escalating cancer burden, but it has a number of resources and expertise for developing the necessary translational cancer research. Fragmentation and lack of sustainability were and still are among the major obstacles to research collaboration in Europe at the time of start-up of EurocanPlatform and there was/is an urgent need for improving cooperation between basic/preclinical and Comprehensive Cancer Centres (CCCs), institutions in which care and prevention are integrated with research and education.
Fragmentation of cancer research in Europe
In 2002 the former EU Commissioner for Research P. Busquin promoted the creation of the European Cancer Research Area at a joint conference by the European Parliament (EP) and the European Commission (EC). European cancer research was “not delivering the outcomes expected by healthcare professionals and citizens; there was a need to create a common European strategy for cancer research”. Encouraged by the outcome of the Conference and continued discussions with the cancer community and the EP, the former Commissioner established a temporary “Working Group on the Coordination of Cancer Research in Europe” to advise the EC and make recommendations on the subject. The mission of the group - chaired by MEP M.V. van Velzen and composed of representatives from clinicians, basic researchers, health authorities, funders, patient organizations, and industry – was to identify barriers to collaboration and find ways to promote the development of partnerships among the Member States. The outcome was a call for proposals in FP6 and subsequent, funding of the Eurocan+Plus project within ‘Integration and Strengthening of the European Research Area’, in 2006. The Eurocan+Plus project is one of the largest ever consultation of researchers, cancer centres, healthcare professionals, funding agencies, industry, and patients’ organizations in Europe. It stressed the need to improve collaboration between basic/preclinical research and CCCs, and proposed to establish a platform for translational cancer research composed of interconnected cancer centres with shared projects to accelerate rapid advances in knowledge and translation into better cancer care and prevention. Two years later, the directors of 16 leading European cancer centres met in Stockholm to define the Platform Concept and discuss steps towards its implementation. To show their commitment, they signed the “Stockholm Declaration”, openly stating their intention to join forces and share resources. The Declaration signalled a paradigm shift that was catalysed by the leadership, commitment, trust, and shared vision of basic and clinical researchers; leading by example! During several preparatory meetings, it became apparent that to move the proposal forward, the scientific community also had to involve cancer organizations and science policy advisers to nurture and accelerate the process. Finally, the EurocanPlatform, a Network of Excellence led by Ulrik Ringborg from the Karolinska Institutet, was funded through FP7 in 2011.
The EurocanPlatform has been a unique collaboration between 28 European Cancer Institutions and Organisations, targeting the whole cancer research continuum from bench to bedside (basic, early and late translational, clinical, epidemiological, implementation in care, and population-based outcomes research) in an effort to improve cancer patient outcomes and reduce mortality. To achieve its objectives, the platform focused on three key research areas: prevention, early detection and therapeutics, as well as to develop long-term sustainable strategies in each area. By strengthening the integration between the different disciplines and stakeholders, the platform with its interlinked cancer centres, common infrastructures, and collaborative projects, has been in a unique position to structure translational cancer research in Europe and to speed up the translation of discoveries into applications that impact patient lives. The consortium had access to the much needed critical mass by large numbers of patients, infrastructures e.g. biobanks with clinical information, bioinformatics, technology platforms, and clinical trial units, which all are prerequisites for successful innovation and to meet the demands of cancer therapeutics. The EurocanPlatform has prioritized structuring actions but also collaborative projects that would facilitate rapid advances in knowledge and their translation into better cancer care, promoting education, training and mobility of young researchers in the area translational research, and disseminate information to society.
Science and technology objectives:
Preventive measures will be key to address the growing number of cancers since treatment cannot be the only solution of the increasing cancer problem. Prevention activities focussed on high-risk individuals and the population at large. The EurocanPlatform aimed at research activities leading to the identification of molecular markers that can identify high-risk individuals and lead to the discovery of marker combinations that pose a relatively low risk but in combination with lifestyle factors, instead would run a substantial risk for the development of cancer in distinct population groups. EurocanPlatform applied el used omics methodologies such as metabolomics and epigenomics to identify and validate biomarkers of exposure for foods an environmental factors suspected to influence cancer risk. Applying the results from these studies into other larger cohorts allows exploring cancer risk factors e.g. BMI and physical activity in different cancers with new biomarkers and molecular pathways involved in tumour progression.
Risk factors for cancer may signify the probability of undergoing (epi-)genetic alterations which subsequently may trigger initiation and subsequent progression into malignant lesions. Identification and diagnosis of premalignant lesions will serve as a basis for surgical programmes and/or medical prevention. Thus a workshop in Chemoprevention (the workshop decided that Medical Prevention is a more relevant term) was performed during the project which resulted in successful grant applications for two studies in colon cancer and breast cancer. Finally, collaborative efforts, which was initiated during the project time, between prevention and therapy fields i.e. IARC and CCCs, will promote the translation of important newly acquired knowledge into prevention programmes conducted at CCCs serving both high-risk individuals and the general public. The two consortia Cancer Prevention Europe and Cancer Core Europe and the strategy of two-way translational research, will together benefit risk individuals and patients in the end.
- Early detection
Early detection of disease gives a window of opportunity of faster treatment when a better treatment effect can be achieved. Premalignant lesions constitute a heterogeneous group ranging from dysplasia to in situ tumours and a subset of these lesions has a high probability of progressing into invasive cancer. A better understanding of molecular pathways underlying progression of premalignant lesions to invasive cancer has the potential to impact prevention strategies. Moreover, the identification of relevant biomarkers for the invasive phenotype will bring opportunities of new diagnostic methods.
Early detection work of the EurocanPlatform included studies of biomarkers in body fluids for screening high-risk groups, detect recurrence, and monitor response using simple body fluid-based assays that could be performed by a general practitioner. Cell-free blood biomarkers of diagnostic and prognostic relevance were identified for lung and breast cancers respectively (with special reference to the triple-negative breast cancer setting, for which is of utmost importance the discovery of new potential molecular targets). Studies of the DNA damage pathway including assessment of the RAD51 assay in biopsies were during the project extended with conversion of both RAD51 and PTEN assays, into assays that work on FFPE material routinely used in clinical practice.
Early detection of invasive disease can also be diagnosed by assessing the presence of tumour cells in the circulation. In the platform a user-friendly approach to isolate and molecularly profile circulating tumour cells was developed and validated for breast cancer during the project.
The main treatment strategy was to develop personalised cancer medicine (i.e. “the right treatment to the right patient at the right time”), based on the knowledge of the molecular mechanisms underlying the disease. This is still the prevalent strategy for which to succeed, treatment predictive biomarkers of primary and metastatic disease need to be identified, as well as sensitive methods to monitor response to treatment and the occurrence of side effects. The mechanisms underlying sensitivity and resistance to anticancer agents constituted an important aspect, since treatment failures often are the result of existing or acquired drug resistance. Preclinical research, closely coordinated with clinical research is required to gain insight into the molecular pathways that drive tumour growth, and to give access to new targets for therapy and consequently development of new anticancer agents. However, major advances can be made by choosing the appropriate combination of drugs, based on extensive diagnostic information gathered by the proposed molecular analyses performed on tumour and normal tissue of individual patients. The strategy of improving treatments will be generic for all tumour diseases.
To analyse molecular pathways the platform shared technologies, resources and competences in collaborations on oncogenic alterations in the kinome in ovarian carcinoma samples obtained pre-treatment, and the DNA damage response pathway, mainly in breast cancer. Another collaborative project is the still ongoing clinical trial in breast cancer, Poseidon, which is performed together with the RATHER FP7 project. The study is linked to preclinical research, and demonstrates the capability of conducting early clinical trials as multicentre collaborations. An important part of the EurocanPlatform project was the prospective validation of target/s and potential biomarkers, which also is being achieved by the Poseidon trial. Here, the translational research validates predictive biomarkers of drug response, pharmacodynamic biomarkers to provide evidence of drug target inhibition, early response biomarkers, and finally biomarkers of drug resistance (both intrinsic and acquired drug resistance) which now are included in the trial.
A fundamental characteristic of the EurocanPlatform project was the linkage between biomarker studies for therapeutics, early detection and prevention. The basic idea is that the altered molecular pathways causing the metastatic phenotypes of cancer are acquired successively and important molecular alterations should be possible to detect in the process from risk factor exposure to manifest disease. For prediction of tumour progression, antitumor and side effects of treatments, multiple biomarkers will be needed to cover relevant altered molecular pathways. Therefore bioinformatics and systems biology approaches are required. Data analyses was performed by the expert bioinformatics group in our NoE. The group brought exquisite expertise in systems biology approaches that was important for the further development of the platform network to facilitate the integration of advanced system biology in clinical research and implementation of best practices. In search of relevant biomarkers numerous technologies were used at the platform such as low coverage NGS genotyping, RPPA protein analysis, proteomics, RNA expression profiling, SNP genotyping, and CNV/LOH determinations. Viability screens were performed, providing a framework upon which candidate therapeutic targets may be identified.
There is histopathological expertise in all the clinical centres. The OECI Biopathology Group will boost the widespread implementation of molecular pathology best practices throughout Europe.
Within the EurocanPlatform a large number of clinical trials were ongoing which could deliver quality assured outcome data and an inventory of clinical trials was made http://ecancer.org/institute/eurocanplatform/clinical-trials.php. The number of trials is huge but so far well-preserved biological materials are available from a limited number of trials. The tools, however, are now in place. Again, the intention with the project was to structure also this area, which has the potential to become a unique infrastructure for discovery and retrospective validation of treatment predictive biomarkers.
The EurocanPlatform had a comprehensive approach, and the final part of the cancer continuum concerned the late translational research, defined here as the trajectory from clinical research to implementation in clinical practice. The goal is that best practices should be swiftly implemented as widely as possible. Our work covered studies among partners comparing implementation of new methods and best practice. However, in order to monitor outcomes of care, detailed and quality assured patient data registries are necessary. Registries should contain information not only on primary diagnosis and treatment, but also treatment of recurrent disease and the occurrence of side effects, to make it possible to properly evaluate the long-term effects of the therapeutic strategies. Patients with recurrent disease and (late) side effects represent a major problem for health care providers as they require long-term surveillance and care. Neither the personnel nor the funds might be available in the future to provide this care. Therefore, there is an urgent need to reduce this burden for both patients and the society. Finally, well-organised clinical cancer registries are not only required to measure the quality of care, but mandatory to evaluate the health economics of the best practices. For such detailed registries, blue prints were developed among partners. Thus a fourth strategy was applied concerning outcomes research. This allows conclusions on whether new treatments are effective and contributes to further optimisation of the use of anticancer agents. It is of great importance to create the detailed registries, which will provide us with the most critical parameters with regard to clinical effectiveness (clinical validation) namely increased life expectancy and quality of life, and costs of new anticancer agents and other treatments.
Education, communication and dissemination
There is a lack of specialised training programmes in translational research. One task of the EurocanPlatform was to set up the Summer School in translational cancer research, together with other organisations/stakeholders. This activity is now annually recurring and serves basic researchers to better understand important clinical questions, while for clinicians it builds knowledge around basic research. Development of MD/PhD programmes with focus on translational cancer research was another objective where EurocanPlatform has performed start up work, which continues within the Cancer Core Europe.
By definition, translational cancer research has the focus on the patient problems. Structuring and co-ordinating translational cancer research should therefore be in collaboration with the patient organisations, which was achieved by the participation of Partner European Cancer Patient Coalition, ECPC. ECPC, the umbrella organisation for the individual European cancer patient organisations, have been involved in scientific coordination for shared views between patients and professionals on research strategies and dissemination processes, as well as biobanking and ethics.
Eurocancercoms set up a well-functioning communication system to coordinate the platform partners, widespread research programmes, and data collections.
WP2 - Cancer risk assessment, prevention and long-term follow-up
WP leader: Christopher Wild, IARC - Partners: KI, IARC, IEO, CHRIS, LUMC
The cancer burden is projected to increase in Europe because of population aging and growth and this will be accompanied by further economic pressure on health care. Therefore the only realistic way to control the cancer epidemic within a sustainable healthcare system is to integrate efforts on prevention with those on treatment. The work performed by EurocanPlatform WP2 made a significant contribution to cancer prevention research in Europe and globally through:
(i) the promotion of translational research involving population based cohorts,
(ii) assessment of genome-wide research for understanding molecular pathways causal for cancer and amenable to intervention,
(iii) development of evidence-based recommendations on breast cancer screening,
(iv) identifying roadblocks and remedies in using cancer registries in translational research,
(v) promoting integration of biomarker-based research into chemoprevention trials, and
(vi) developing a plan for a Cancer Prevention Europe initiative to complement the advanced progress with Cancer Core Europe.
Promote translational approaches bridging population based cohorts and studies on biomarkers of risk and early detection of cancer.
WP2 has been involved in setting up methodologies based on omics approaches and large-scale population-based cohorts. Omics methodologies included the development of metabolomics and epigenomics. Metabolomic methodologies based on high-resolution mass spectrometry have been developed for the identification and validation of biomarkers of exposure for foods and environmental factors suspected to influence cancer risk. These methodologies have been applied to dietary intervention studies and to cross-sectional study in the European Prospective Investigation on Cancer and nutrition (EPIC) study and new biomarkers of intake for various beverages, fruits, and meat have been discovered in urine and blood (Edmands et al., 2015; Cheung et al., 2017). These markers of intake are now applied in other large cohorts to study their associations with various cancers and cancer risk factors such as BMI or physical activity. In addition, development and application of epigenomics methodologies by WP2 allowed investigation of the potential of epigenetic changes in pre-diagnostic peripheral blood samples as a marker of exposure to tobacco smoke and cancer risk in EPIC cohort. These studies revealed that cigarette smoking has a broad impact on the epigenome that, at many genomic loci, persists many years after smoking cessation. Many of the genes altered by smoking-induced epigenetic changes were novel with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Epigenetic marks at these genes could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke (Ambatipudi et al., 2016; Joehanes et al., 2016; Ambatipudi et al., 2017). Eight original papers describing the development and application of metabolomics and epigenomics methodologies to population-based cohorts have been published in peer review journals. Together, these advances demonstrate how the application of methodologies developed by EurocanPlatform partners to population-based biobanks may promote translational research bridging European population-based cohorts and discovery of biomarkers.
Assessment of genome-wide research for understanding molecular pathways causal for cancer and amenable to intervention.
The position paper “Genomics of Cancer and a New Era for Cancer Prevention” was prepared by IARC scientists and published in a peer review journal (Brennan and Wild, 2015). The paper discusses how recent studies of the genomic profile of tumours could help to identify new carcinogens and may subsequently result in implementing strategies that limit exposure. In addition, it argues that it may be feasible to utilize genomic biomarkers to identify cancers at an earlier and more treatable stage using screening or other early detection approaches based on pre-diagnostic biospecimens or liquid biopsies. Finally, the paper proposes that the potential of this new knowledge and its successful outcome will depend on international collaboration and planning similar to that of recent sequencing initiatives.
Development of evidence-based recommendations on breast cancer screening.
To develop evidence-based recommendations relevant to breast cancer screening WP2 organized three working group meetings, two at IARC in Lyon and one in Rome. The participants included professionals and researchers from the fields of pathology, radiology, surgery, gynaecology, oncology and epidemiology. Key recommendations addressed at the meetings included: (i) regularly reporting an accurate preoperative and postoperative description of tumour distribution, (ii) complete histopathologic assessment of surgical margin, (iii) reporting apparent site of tumour origin to optimize treatment, (iv) routine inclusion of mammographic tumour features as an important prognostic factor, and (v) investigation of ‘neoductgenesis’, an important new prognostic feature for breast cancer. The working group developed a scientific report aiming at improving the multidisciplinary management of breast lesions. The report will be submitted for publication in a peer-reviewed journal.
Roadblocks and remedies in using cancer registries in translational research.
Cancer registries provide a population-based infrastructure for evaluating and comparing cancer preventive and therapeutic interventions. Involvement of cancer registries in translational research, the linkage with cohort biobanks and the dynamic use of the cancer registry information to improve health management, clinical trials and follow-up, offers much potential. To realise this potential fully, registries must not merely be seen as data repositories, but as active participants in information collection, standardisation and linkages with other existing datasets. In 2012, IARC organized an expert group meeting to explore this potential, and provide specific examples of good practice, in order to inform stakeholders. It also discussed barriers and roadblocks in using cancer registries in translational research and proposed remedies for the successful implementation of research using population-based cancer registries.
Biomarker-based chemoprevention/ medical prevention trials.
Cancer chemoprevention is the use of natural or synthetic agents to reverse or inhibit carcinogenesis at the preclinical stage. Chemoprevention requires the selection of at-risk population based on measurable risks factors as early as possible along the multiphase process of carcinogenesis. In 2014, WP2 organized the expert group meeting biomarker-based chemoprevention trials in Europe, held at the European Institute of Oncology (EIO), Milan, Italy. It was decided to replace “chemoprevention” with “medical prevention”. The group discussed ongoing projects on medical prevention led by EIO and explored how medical prevention trials may provide an access to large series of specimens for discovering and validating novel biomarkers. This resulted in new multidisciplinary initiatives that applied the novel methodologies developed by IARC (metabolomics and epigenomics) to research projects aimed at elucidating the clinical and molecular effects of medical prevention agents in patients at high risk for cancer. Successful grant applications to the ERA-NET Translational Cancer Research (TRANSCAN) scheme (approved in 2014), enabled the development of two multidisciplinary studies on medical prevention involving partners from the EurocanPlatform consortium: (1) a multicentric case-control study on colorectal cancer/adenoma and (2) a medical prevention trial with metformin in breast cancer survivors.
European cancer prevention coordination and strategic position paper.
WP2 organized the workshop “Cancer Prevention Europe” (held at IARC in 2015) with a view to obtain a clearer vision and strategy in relation to cancer prevention across Europe. IARC gathered leaders in cancer prevention to discuss major gaps and opportunities in cancer prevention in Europe and identify major stakeholders. The group also discussed the next steps needed in order to implement the strategy in the coming years. This led to the production of a position paper describing a sustainable way to develop cancer prevention in Europe. The position paper outlines a proposition to create a stable Cancer Prevention Europe consortium to foster coordination, research and training devoted to prevention. In analogous fashion to Cancer Core Europe this consortium would begin with a relatively small number of key partners to help shape the agenda. This initiative aims at a more long term action plan to pursue the mission of prevention and a sustainable infrastructure in Europe. The activities within cancer prevention could comprise the following areas: cancer registration; cancer aetiology; evaluation of preventive interventions (primary, secondary, tertiary) in randomized trials and observational studies; and implementation research to enhance the effectiveness of intervention programmes. A number of leading cancer research institutions have already agreed in principle to co-fund this initiative for a two-year period in the first instance through a consortium agreement which includes a defined set of deliverables. The latter agreement is currently circulating among the partners prior to signature.
WP3 - Early detection/biomarker discovery
WP leaders: Anne-Lise Børresen Dale / Åslaug Helland, OUS, & Maria Grazia Daidone, INT
Partners: KI, Inst Curie, DCS, OUS, INT, DKFZ, IGR, IARC, UOXF.HD IEO, CHRIS, NIO, UCAM, IJB, LUMC, FIVO
In this era of personalized medicine, validated biomarkers are instrumental. The drug development offers new anticancer agents at high speed, and their costs are extreme. There is an urgent need for robust biomarkers to identify which patients will benefit most from the specific drugs. Patients with low chances of effect of a specific treatment can be treated otherwise, and patients with a high likelihood of response, can benefit from the specific new drugs. This personalising of cancer treatment would be of huge benefit for the patients. In addition, the costs related to the use of drugs would be reduced, as only the subset of responsive patients would be treated with the right drug at the right dose and at the right time. These studies, aiming at restricting an inappropriate use of new drugs, is not prioritised by the pharmaceutical companies, and need to be focused on in the public sphere. Moreover, molecular screening by NGS highlighted the spatial and temporal heterogeneity of solid tumours as well as the clonal evolution of cancer cells during progression and under treatment pressure. Such findings question whether an optimal assessment of disease progression and a screening for druggable mutations should be based on molecular features of primary or recurrent/metastatic lesions and therefore represents a crucial element for failure or success of personalized medicine. In fact, new targeted therapies may induce only short-term benefit annulled by the emergence of resistant clones with new driver mutations, which would need to be rapidly and potentially identified. Serial tissue sampling is therefore essential but, unfortunately, also represents a problem since biopsies from solid lesions, which are invasive and potentially painful and risky, cannot be easily repeatedly sampled or are inaccessible and may not fully reflect tumour heterogeneity. The need to early detect and strike this “moving target” is now directing the scientific community towards liquid biopsy-based biomarkers, which include circulating tumour cells (CTC) cell-free circulating nucleic acids (i.e. circulating tumour DNA, ctDNA, and microRNA, ctmiRNA), that can be repeatedly assessed through non-invasive and easy-to-perform procedures and may act as reliable read-outs of functional and molecular features of recurrent/metastatic lesions. In addition, knowledge about prognosis or likely course of disease is important in treatment stratification. The technologies will be used for classification of premalignant lesions and early invasive tumours. Identification of relevant premalignant lesions will open up for new strategies for early treatment.
The five years of work within the EurocanPlatform, has been instrumental to establish and confirm the network of collaborations within WP3 and – at large – with other EurocanPlatform participants to strengthen a multidisciplinary approach, and to challenge assays/biomarkers/omics analyses and data interpretations to provide clinicians with tools for an effective integration of biomarkers in clinical trials. Such improvements were obtained thanks to the increased identification of clinically relevant signatures/biomarkers derived from tissue and liquid biopsies to be validated at a multicentric level, and to the willingness to share biological specimens and datasets among the WP3 participants. Specifically, cell-free blood biomarkers of diagnostic and prognostic relevance were identified respectively for lung and breast cancers (with special reference to the triple-negative breast cancer setting, for which is of utmost importance the discovery of new potential molecular targets), and a user-friendly approach to isolate and molecularly profile CTCs was developed and validated for breast cancer. mRNA and miRNA signatures associated to breast and lung cancer progression as well as to response to systemic treatments are currently under multicentric validation, and bioinformatic approaches to integrate molecular information are under development for these tumour types. A pilot study evaluating the diagnostic potential of ctDNA was carried out on an historical series of stage I and II breast cancer with a follow-up longer than 20 years. The presence of mutated ctDNA, resembling DNA mutations detected in the primary tumour at time of initial diagnosis anticipated the diagnosis of new disease manifestations (both at local and distant sites) up to 22 months compared to clinical and radiological examinations, while ctDNA was undetectable up to 180 months of follow-up in plasma samples of patients with no evident disease. Such results prompted the activation of prospective trials to confirm the predictive accuracy of ctDNA.
Within the EurocanPlatform, we have identified different molecular subgroups of lung cancer with differences in clinical course. These findings have been published in several research papers. Differences in methylation in adenocarcinomas impacts the prognosis significantly. In addition, specific microRNAs have prognostic influence as well. We have identified a microRNA signature in serum samples differentiating lung cancer patients from patients with COPD and healthy controls. Early diagnosis of lung cancer has a major impact on prognosis, and screening of high-risk heavy smokers are discussed worldwide. A serum-signature used in combination with radiology could increase sensitivity/specificity of the radiology alone, increasing the effectivity of screening. These projects were done in collaboration with researchers in the EurocanPlatform. Follow-up studies are ongoing.
Analyses on interstitial fluid in breast cancer could lead to identification of important biomarkers, which could be detectable in circulation. Several analyses have been performed on breast cancer interstitial fluid, and two papers have been published, while some work is still ongoing.
WP4 - Kinome analyses to guide therapy choice
WP leader: René Bernards, NKI - Partners: Inst Curie, NKI, UCAM, EMBL
WP4 initiated this study with the aim of finding new therapeutic target for high-grade serous ovarian carcinoma (HGSOC), one of the most lethal gynaecological malignancy in western countries that accounts for almost two-thirds of ovarian cancer deaths (Mittempergher et al 2016. Transl Oncol). We used next-generation sequencing (NGS) to sequence kinase genes and additional cancer-related genes using an exome-capture enrichment strategy so called kinome sequencing. We focused on the family of kinases as these enzymes are excellent targets for therapy and many kinase inhibitory drugs are already validated in various stages of clinical development.
A cohort of 127 patients with high-grade serous ovarian carcinoma (HGSOC) and matched normal samples was analyzed with kinome sequencing. The most frequently mutated genes in the HGSOC ovarian sample set are TP53 and BRCA1. Other genes were mutated at lower frequency (<3%), as was the case of JAK3 gene. Functional validation of JAK3 mutations in a cell line model showed a potential oncogenic activity of a novel mutation in the kinase domain of JAK3. Additional experiments to further validate function and assess sensitivity to drug (such as JAK-inhibitors) of this novel mutation are ongoing. Sequencing analysis of additional 575 FFPE HGSC samples with matched normal from Cambridge and Curie institutes revealed 19 somatic mutations in JAK3 (3.9%), however only 2% showed potential damaging effect. Additionally, 119 samples were processed in RPPA (Reverse Phase Protein Assay). We identified 11 epitopes able to stratify our patient population in two groups based on the activation status of the PI3K pathway; activated or not activated PI3K. Together with the kinome sequencing and the RPPA analyses, we have developed interphase FISH assays as gold standard controls for copy number changes using MYC, TERC, and SE7 control probes. We have developed novel statistical methods for copy number counting based on the FISH data and evaluated the use of SNP calls from the kinome sequencing data to estimate loss of heterozygosity in the shallow (low-coverage) whole genome data to infer absolute copy number.
WP5 - Targeting the DNA damage response
WP leader: Chris Lord, ICR - Partners: DCS, NKI, ICR
WP5’s main achievements can be summarised as follows:
1. Conversion of both RAD51 and PTEN assays into assays that work on FFPE material routinely used in clinical practice
2. Assessment of the RAD51 assay in biopsies obtained from breast cancer patients treated with anthacycline-based chemotherapy
3. Assessment of the RAD51 assay in biopsies obtained from xenografted tumour samples with correlative PARP inhibitor sensitivity data
4. Development and validation of a tumour PTEN assay
5. Generation of functional viability profiles for a panel of breast tumour cell line models as well as comparison non breast tumour cell line models
6. Analysis of genetic dependencies in breast and other cancer types via interrogation of functional viability profiles
7. Identification of synthetic lethalities for breast and other tumour types with loss of function ARID1A mutations
8. Use of genetic dependency data from (6) to identify novel synthetic lethal targets that operate in cancer
9. Generation of an integrative, searchable dataset describing kinase genetic dependencies in cancer
10. The identification and validation of PARP inhibitor/ERCC1 synthetic lethality and the drafting of a clinical trial protocol aimed at assessing the utility of PARP inhibitors in cisplatin sensitive non-small cell lung cancer
WP6 - Therapeutic strategies
WP leaders: Josep Tabernero, VHIO - Partners: KI, OUS, CNIO, INT, DKFZ, IGR, UOXF.HD IEO, CHRIS, NIO, NKI, ERASMUS MC, UCAM, IJB, VHIO, EORTC
The need to speed up and make more coherent, efficient and integrated the overall process of targeted drugs development is obvious and should result in a shift in the design, strategy and methodology of phase I and early phase II trials, as well as proof-of-concept trials of biology-driven therapeutic-decision. This necessitates revising the conventional partnerships between the academic world and pharmaceutical industry, which is urgent at the European level to increase competitiveness and assure access to innovative therapies for patients in Europe. The overall aim of WP6 has been to demonstrate the importance and relevance of an integrated network of large Comprehensive Cancer Centres in this paradigmatic shift. WP6 was dependent on the biomarker discovery in WP 3, 4, 5 and 7. WP6 also had the mission to follow the total development of new biomarkers for implementation into prospective validation and clinical trials.
The overall goals of the Workpackage were i) to provide a strong basis to introduce systems biology into cancer treatment towards personalised medicine, ii) to modify at the European level the strategic dialog in between academia and pharmaceutical companies, iii) to offer new concepts for drug development.
To ensure the compliance of these objectives, a Clinical Steering Committee (CSC) was created in May 2011. It is composed of relevant figures from all clinical partners. During the initial CSC meetings the common needs and goals of EurocanPlatform teams involved in early drug development and biomarker driven clinical trials were discussed and identified:
1. Increased and facilitated access to tumour material (repeated access through biopsies, tumour material surrogates).
2. New paradigm for evaluation of tumour response (imaging) beyond the RECIST evaluation at a fixed time point.
3. Development of innovative designs for phase 1 and for phase 2 trials.
4. Systematic tumour molecular profiling for patients entering a phase 1 or 2.
5. Use of pangenomic profiling to go beyond the companion biomarker approach developed by Pharma.
6. Strong integrating bioinformatics program.
7. Capacity to run company independent trials (IST) and facilitation of regulatory issues for trials authorisation.
8. Address the issue of ethics, quality, SOPs and cross validation of technical assays when patient samples have to be analysed.
Also, the medical and scientific prospective for this clinical research program was defined as follows: To address drug combinations based on a strong preclinical rationale through investigator driven clinical trials that will include systematic pangenomic molecular profiling monitoring (pre, post and at progression) and integration of biological and clinical data.
Guided by these recommendations, some potential clinical trials were identified, and one of them was defined and executed during the EurocanPlatform project: The phase I/II POSEIDON trial. This clinical trial aims to evaluate the benefit of combined use of Tamoxifen plus Taselisib in metastatic breast cancer patients. Since there is no prior evidence in combining these two therapies, a phase Ib trial for safety and toxicity assessment has been performed, followed by a phase II randomized trial to assess the benefit, in terms of Progression Free Survival, of the combination.
More in detail, the phase Ib trial of the POSEIDON enrolled 30 patients between November 2014 and January 2016 in three dose levels (2 mg intermittent schedule, 4 mg intermittent schedule, 4 mg continuous schedule). There are no patients on study treatment anymore; the last patient progressed in December 2016. Average time on treatment was 5.8 months. Preliminary results were sent and accepted for poster discussion to the 2016 ASCO meeting, and likewise accepted poster at SABSC 2016. Currently we are investigating the pharmacokinetic data of the two drugs, the presence of PIK3CA mutation as marker for response and the fraction mutant ctDNA as early marker of response/resistance. The team is already working on a paper to communicate the final analysis of the results, including the translational results. The participating partners in the phase I trial have contacted other centres, with high recruitment capacity, to ensure that they are ready to participate in the phase II. Additionally, feasibility assessment has been performed in other centres. Each participating partner has contacted the most suitable centres on theirs country.
Other relevant outcomes of the trial that demonstrate the partners’ capacities to lead this kind of initiative are:
- Biopsies from 10 out 30 patients were obtained to perform molecular studies (an impressive data when compared to competitive trials promoted by pharma companies).
- The recruitment rate of the trial was performed within a reasonable timing (demonstrating that clinical trials with academic leadership can be competitive despite restrictions).
An important deliverable from the collaboration between centres on development of therapeutics is the Cancer Core Europe aiming at a sustainable consortium for development of personalised cancer treatment. Thus, in the last year of EurocanPlatform a new clinical trial called Basket of Baskets has started. Developed under the Cancer Core Europe umbrella, Basket of Baskets, is a modular study (sponsored by VHIO on behalf of CCE) where all the partners in CCE will lead at least one module. BoB includes a molecular profiling program (iPROFILER), following CCE standard operating procedures (SOPs) for patients with advanced solid tumours; and a modular, investigator initiated basket study (iBASKET) for patients with selected molecular alterations.
The iPROFILER will align molecular prescreening platforms and bioinformatics in order to have all six sites performing the same prescreening analysis. The iBASKET will consist on a modular protocol with common inclusion/ exclusion criteria. Each module, which could be incorporated to the main protocol any time if funded (by the pharmaceutical industry), will explore number of arms evaluating a targeted agent in patients with defined molecular alterations. A virtual tumour board will assist physicians in the recommendation of therapy/module, based on high-density molecular data.
At the moment there are seven arms under negotiation with four different pharma companies and the first arm has already been funded by the pharmaceutical industry.
WP7 - Mouse Tumour models
WP leader: Mariano Barbacid, CNIO - Partners: Curie, CNIO, NKI, UCAM
The aim of WP7 was to generate mouse tumour models including PDX, that at the pathological and molecular level closely reproduce the natural history of the main human tumour types and use these tumour models for validation studies with the ultimate goal to determine their predictive value for subsequent clinical trials.
Breast cancer is the most common malignancy in women worldwide, affecting 10-12% of the female population with over 500,000 deaths per year. To study the role of defined mutations in breast cancer development and progression, a genetically engineered mouse models of human breast cancer was generated for BRCA1- and BRCA2-associated hereditary breast cancer, and E-cadherin mutated lobular breast carcinoma. We have used these models for preclinical tumour intervention studies with (combinations of) targeted therapeutics with the ultimate aim to develop optimized combination treatments that lead to complete tumour eradication. Progress has been made on the development of biomarkers. We have uncovered mechanisms resulting in drug resistance to CisPlatin and PARP inhibitors in a subset of breast cancers that will help us to overcome resistance in the cognate human tumours ( ). In the generated PDX (patient derived xenografts) models from the POSEIDON clinical trial (Bruna et al. 2016, Cell), studies show that:
- PDXTs and PDTCs have preserved intra-tumour heterogeneity.
- PDTC drug responses in vitro are predictive of PDTX drug responses in vivo.
- Drug responses are preserved across passages.
- Integrative analysis reveals novel pharmacogenomics biomarkers.
Lung cancer is the most common cause of cancer-related death worldwide. We have addressed this problem by investigating the nature of the cell of origin in two of the most prominent cancer subtypes, i.e. Small and Non-small lung cancer (SCLC and NSCLC), as well as developed more aggressive mouse models for in vivo validation of putative therapeutic targets. Progress has been made with regard to development of a suitable intervention model for SCLC. We have also developed a genetic approach to identify potential targets to treat NSCLC. Thanks to this approach, we have established that not all the Raf kinases play the same role in mediating K-Ras oncogenic signalling at least in NSCLC. c-Raf has been validated by genetic means as an effective therapeutic target for established K-Ras-driven NSCLC. These findings suggest that selective c-Raf inhibitors should have therapeutic activity in NSCLC, one of the human tumour types with worse prognosis and for which there are no selective treatments.
We have also identified the cell of origin in K-Ras driven lung adenocarcinomas as the SPC+ alveolar type II pneumocytes. Two K-Ras downstream kinases, Cdk4 and c-Raf, have been validated as useful therapeutic targets in PET positive NSCLC tumours. We have shown that both Myc and Nfib overexpression accelerate SCLC development. In addition, Nfib causes tumours to metastasize more effectively.
WP7 have focused in the generation and characterization of patient derived xenograft (PDX) models of K-Ras mutant lung tumours. In this study, we have identified the DDR1/NOTCH signalling pathway as a potential therapeutic target in K-RAS mutant lung adenocarcinomas (Ambrogio et al. 2016, Nature Medicine).
In pancreatic cancer (PDAC), treatment with anti-inflammatory drugs or ablation of the Cox-2 locus results in significant improvement of the tissue parenquima but not in increased survival. On the hand, concomitant ablation of c-Raf and EGF receptor prevents the development of PDAC tumours even in the absence of the p53 tumour suppressor. We have developed a new FLpase-based model of K-Ras/p53 driven PDAC model and tested the effect of blocking c-Raf and EGF receptor signalling in well formed PDAC tumours to evaluate their potential use in the clinic. Inhibition of c-Raf and EGFR appears effective in preventing mutant-Ras-driven pancreatic adenocarcinomas. Furthermore, PDX models of pancreatic tumours are underway.
Altogether, the mouse models generated in this consortium are now extensively used to design and validate a diversity of targeted therapies and combination therapies in several highly prevalent cancers. Overall, the integration of preclinical and early clinical research has been improved during the project time, both within Comprehensive Cancer Centres and between basic/preclinical and clinical cancer research centres. Important clinical questions have been addressed to the preclinical research laboratories.
WP9 Bioinformatics/integration of information for pathway control
WP leader: Jan Korbel, EMBL - Partners: IGR, EMBL
Genetic variation is a fundamental reason why humans differ from one another and why some individuals are more susceptible to diseases, such as cancer, than others are. Thanks to improvements in the sequencing technology, the numbers of sequenced cancer genomes steadily have increase and with this, most notably cancer genome sequencing has enabled new insights into how tumours evolve. For making the maximal use of cancer genomics data in research and translation, the development of bioinformatics tools, resources and protocols for collecting, processing, integrating, and analyses are fundamental. Therefore, scientists involved in WP9 have developed and further optimized novel computational approaches for accurately detecting and characterizing cancer-associated genomic structural rearrangements (SRs) in DNA and RNA sequencing data, which were shared among the EurocanPlatform community. Furthermore, we developed a cloud-based framework for performing theses analyses. This WP also developed protocols for a data collection, management and access system to be used within the EurocanPlatform.
Applying these new SR characterization approaches facilitated important scientific advances. For example, studies led by WP9 scientists have yielded novel insights into androgen-driven DNA rearrangements in prostate cancer with early disease onset (Weischenfeldt et al. 2013, Cancer Cell). Standards for data analysis, namely the characteristics for specific rearrangement pattern called chromothripsis, a one-off chromosomal shattering which is relevant for cancer prognosis in cancer genomes has also been established (Korbel & Campbell 2013, Cell).
We also performed analyses across cancer types and subtypes including a currently incurable leukemia subtype, the TCF3-HLF-positive acute lymphoblastic subtype of acute lymphoblastic leukemia (ALL). Using an integrated approach, we have uncovered distinct mutation-, gene expression- and drug response- profiles in these cancers and treatment-responsive TCF3-PBX1-positive ALL. We were able to identify recurrent intragenic deletions of PAX5 or VPREB1 in conjunction with the fusion of TCF3 and HLF. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Furthermore, notable on-target sensitivity was achieved, in particular, with the BCL2-specific inhibitor venetoclax (ABT-199), which hence is suggested as a new treatment option for TCF3-HLF-positive ALL (Fischer at al. 2015, Nature Genetics).
Recently, we implemented a new approach to systematically identify enhancer hijacking in a pan-cancer analysis (that means across many different tumour types). This approach is based on integrating transcriptome sequencing (RNA-Seq) and somatic copy-number alteration (SCNA) profiling data. Applying our framework, we observed numerous recurrent SCNAs in association with the marked dysregulation of known or candidate cancer genes in cis. Systematic analyses were performed as part of this study (Weischenfeldt et al. 2017, Nature Genetics) and implicate numerous DNA rearrangements in cis of cancer census genes as candidate drivers. These findings implicate enhancer hijacking in cancer gene activation in numerous solid tumours, and show an entirely new way to systematically catalogue and characterize somatic driver alterations in cancer genomes. This work was performed in collaboration with Åslaug Helland (Partner Oslo University Hospital).
Most recently, we found an upregulation of proliferative gene expression signature in tumours with either a high load of point mutations or somatic copy number alterations (Buccitelli et al. 2017, Genome Research). Currently, we are extending our pan-cancer based analyses to tumour-focused analyses of germline variation in medulloblastoma patients, and also across several tumour types, results which we envision will likely be translatable into the clinics to improve patient counselling and risk stratification (Waszak et al. submitted).
With a switch from microarrays to RNA sequencing (RNAseq) based gene expression analysis technology we also worked to assess existing and to develop new bioinformatics methods for RNAseq data analysis. In particular we performed the RNA sequence mapper assessment and based on it developed a new gene fusion discovery pipeline. We used it jointly with René Bernards’ group in the Netherlands Cancer Institute to apply this method to lung cancer data, which led to discovery of a new recurrent fusion gene (Majewski et al. 2013, The Journal of Pathology).
We also worked jointly with Partner Oslo University Hospital to analyses micro-RNA data and recovered pathways Involved in lung adenocarcinomas (Haakensen et al. 2015, Journal of Thoracic Oncology) and to look for micro-RNA signatures in breast cancer progression (Haakensen et al., 2016, International Journal of Cancer).
On the database development side, after extensive analysis of the user requirements during the first year of the project it was decided that the EurocanPlatform database should unitize the existing bioinformatics infrastructure within EBI. Therefore the EurocanPlatform database was developed utilizing the EMBL-EBI’s BioStudies Database infrastructure (McEntyre et al. 2015 Molecular Systems Biology) where all relevant public data from the project partners were collected and made available (http://www.ebi.ac.uk/biostudies/EurocanPlatform/studies/). The selected datasets were also disseminated via the ArrayExpress functional genomics archive (Kolesnikov et al. 2015, Nucleic Acids Research) and reprocessed in the EMBL-EBI’s Expression Atlas (Petryszak et al. 2016, Nucleic Acids Research).
WP10 - Biobanking
WP leader: Peter Riegman, ERASMUS MC - Partners: KI, Inst Curie, OUS, CNIO, INT, IARC, IEO, CHRIS, NIO, NKI, ERASMUS MC, UCAM, FIVO, OECI, EORTC
Translational cancer research is key for the innovation of patient care and is at the heart of the new way of thinking in terms of personalized or precision medicine. In many cases translational research can only be performed with biological materials derived from patients. Such materials need to be collected and preserved in biobanks and used for medical research. However, practice has shown that the collection and conservation process of sample and data, as well as the governance, regulations and ethics involved when using human biological materials for research purposes, need to be very well organised in a good infrastructure. This is especially key when the demand of statistical significant research drives for high sample numbers and cooperation in multi centre research projects is planned.
The EurocanPlatform biobanking workpackage would build upon already developed experiences make the human biomaterials efficiently available for the scientific community including the EurocanPlatform consortium.
Several approaches were taken where the highlights and the results are mentioned here:
- Access rules were studied and set to stimulate sample exchange in multi centre research projects in a recommendation.
- An inventory of win-win situations were made and described to stimulate the field into cooperation.
- The influence of quality of samples used on sample exchangeability and reproducibility of results, which resulted in participation in writing CEN and ISO technical specification in diagnostic sample collection. CEN publications on the pre-analytical phase blood, frozen tissue and formalin fixed tissue, where DNA, RNA and proteins are considered separately as input for the analytical test. These documents are expected to be released on the ISO level in the coming year.
- Patient cancer organisation ECPC was consulted on how to best involve patients in the biobanking process. This resulted in a ‘frequently asked questions’ on biobanking with questions from patients and answers that were put into understandable language for patients. In addition, the view of the patient was discussed on the consent issues, where the use of biomaterials was concerned.
- Participation and lobbying in the introduction of the new European GDPR to ensure a continuation of the translational cancer research involving data and human biomaterials.
- A ‘Letter of Intent’ was written and sent to all member CCC of EurocanPlatform and the OECI community, where the impact of board decisions on sample exchangeability of collected biomaterials and data was explained in terms of access rules, impact factor and sample quality.
- The TuBaFrost sample exchange platform was updated to the current needs and wishes of the consortium.
- A comprehensive view on cancer biobanking was developed within WP10 when working on the ambitiously set program. This comprehensive view have been disseminated in publications and presentations. Moreover all the important findings that were described in the WP10 deliverables were also shared completely with BBMRI-ERIC, which represents the European biobanking community.
WP11 - Clinical Epidemiology
WP leaders: Hermann Brenner & Petra Schrotz-King, DKFZ - Partners: KI, Inst Curie, DCS, OUS, INT, DKFZ, IARC, RORENO, IEO, CHRIS, NIO, NKI, ERASMUS MC, UCAM, IJB, VHIO
In WP11, the major efforts were concentrated on progress towards establishing a harmonized clinical cancer registration infrastructure and shared core resources on breast, colorectal, gastric and pancreatic cancer. As a first step, in order to create a tool to help the assessment of clinical cancer registration activities, four questionnaires were designed to collect information on the general situation of clinical cancer registration at WP11 participating centres. The questionnaires included a general, a data availability, a follow-up, and a biobank questionnaire. By the end of the first year, substantial amount of information was collected from a number of participants via both returned questionnaires, as well as exchanging information through emails and telephone calls.
Although some type of clinical cancer registration had been established or was being established in many of the centres, heterogeneity in type, structure and extent of data collected was found to be large, and key data elements needed for comprehensive outcome research were often lacking. In order to promote establishing the structures needed for such comprehensive outcome research, blueprints on the data elements needed for such research were developed, discussed and agreed upon between partners for several of the most common cancer entities including breast and colorectal cancer.
At the same time, several pilot studies using already available data across WP partners were designed in order to demonstrate the use of comparative cancer care and outcomes research for monitoring and enhancing translation of therapeutic innovation into clinical practice, using key innovations in breast and colorectal cancer as examples. Proposals of these studies were discussed within the regular annual WP11 meetings. Through the EurocanPlatform collaboration, we could successfully develop a European network of comprehensive and standardised cancer databases, comprised of clinical and epidemiologic data elements, diagnostic and therapeutic modalities, and indicators of cancer care utilisation.
During the project period, several successful pilot studies have been conducted on innovative treatment modalities of most common cancer entities in diverse patient populations and the impact of these innovations on outcomes of patients in routine clinical practice. Key examples include the uptake of therapeutic innovations in breast cancer and colorectal cancer surgery, neoadjuvant and adjuvant treatment. The most interesting results of these pilot studies, which often showed striking variation in cancer care modalities between countries and centres with major impact on outcomes, are already published or close to submission to international journals.
During the the project period, we could steadily expand and intensify our data networking with EurocanPlatform partners from main European population-based and clinical cancer registries, as well as external partners including other major cancer consortia such as EUPancreas, DOCG (Dutch Pancreatic Cancer Group), EURECCA (acronym for EUropean REgistry of Cancer CAre or EURopEan CanCer Audit), and other leading European cancer centres. The partners of WP11 have shown outstanding commitment in establishing this international network, which encouraged us to continue these unique collaborative activities beyond the project period under the lead of the German Cancer Research Centre (DKFZ).
WP12 - Quality assessment, accreditation and metrics
WP leaders: Mahasti Saghatchian, IGR, & Wim van Harten, NKI - Partners: IGR, IEO, NKI, OECI
During the project we have developed and piloted an Excellence Designation System (EDS) in the EurocanPlatform project (Rajan et al.2015 Mol Onc). The EDS contains a set of “excellence criteria” and a (formal) governance mechanism to identify and assess excellent translational research in European Comprehensive Cancer Centres (CCCs). The rationale for EDS is twofold: First, to formally and transparently select CCCs that qualify for excellence, e.g. to join new dedicated platforms (such as ultimately, a virtual European Cancer Institute). Second, to motivate and improve the performance of CCCs. The European Academy of Cancer Science is the designating body and two centres are under evaluation during spring 2017.
Another objective was to develop a set of indicators to measure the production and activity of the translational research performed on the platform in terms of scientific and societal value. The set of indicators (selected after a systematic literature review, a qualitative study and a Delphi survey) used a mix of relevant existing and new indicators with focus on the outcome of research on patients or public health (Thonon et al. 2015, Health Res Policy Syst). These indicators were then applied in a bibliometric study to measure the production and impact of the research carried out in 17 cancer centres in Europe (Thonon et al. 2015, PLoS One). The report address three aspects of research outcomes: scientific production and impact; collaboration (national, international and intra-disciplinary) and impact on health service and patient care (use of research in guidelines and policies).
Finally as an extra undertaking we developed patient-centred indicators in oncology to explore potential patient centred care indicators for cancer patients and selected those that could be used for evaluation of Comprehensive Cancer Centres. From this work several promising quality indicators were identified (especially the survival rate, coordination of care, time and information indicators) that could be useful to improve patient centred care in Comprehensive Cancer Centres.
WP13 - Education and Training
WP leader: Angelo Paradiso, NCI-Bari - Partners: NIO, NCI Bari, ECCO, OECI
Education and training is an important component of the comprehensive cancer activities, e.g. basic/specialist training of staff, research education, continuous medical education as well as education of patients and relatives. With the growing complexity in cancer care, advanced research educational courses are urgently needed, and it is presently difficult for individual centres to offer state-of-the-art research education courses across the complete cancer continuum. Today, more biologists than MDs go into cancer research and it is important to stimulate medical students to move into research by providing a new type of education that is tailored to their needs. Moreover, the gap between basic/preclinical and clinical research must be filled in order to stimulate collaborations and innovations. Joint educational activities may increase the possibilities to meet new challenges if a state-of-the-art education in translational cancer research is provided.
In 2011, WP13 performed an analysis of all the educational events offered in the cancer research field by the members of the EurocanPlatform, both institutes and organisations. The dominance of basic science areas in the educational scenario was highlighted, but the perhaps most significant result of the analysis was the lack of multidisciplinarity. In terms of the training of professionals, there was a notable divide between the different areas of the translational research continuum - basic, clinical and outcome research. Furthermore, the analysis showed that there was a need to highlight the emerging area of personalised medicine as well as more patient/case-focused events rather than topic-focused.
The EurocanPlatform Education Working Group was created to incorporate more diverse educational expertise into the WP work. One topic that the group discussed was possibilities for sharing educational resources among centres to ensure equal quantity and quality of training for all. While the group could conclude that in order to use resources already produced by individual centres as part of their individual education programmes to create a virtual portfolio to be shared via e-learning platforms, improved communication about events was desired. Another point of discussion was the possible creation of new events in key areas to cater for topics/professionals that had been identified as under-represented and to begin to implement multidisciplinarity and a greater focus on patients in training events. Although E-learning options could resolve many problems of education accessibility and budget for the learner, creation of the materials would require either effort and budget not currently available, or contributions on a voluntary basis. Furthermore, a proposal for a new model of experimental education event was drawn up which not only caters for the need for professional multidisciplinarity, but also has universal appeal whilst bearing in mind diverse local realities. Ultimately, it became evident that before proceeding it would be necessary to determine their usefulness and appeal for the eventual learners. Thus a detailed educational needs survey and analysis of the satisfaction levels and needs of learners within the platform with regard to the current educational scenario in Europe was conducted in collaboration with WP14. Some main points collected from the survey were:
- The interest in post-graduate education is high; (many responders already held a post-graduate qualification or indicated they would be interested in obtaining one);
- The main reasons for researchers/healthcare professionals not pursuing post-graduate qualifications or regular education opportunities are a lack of time to dedicate to education and a lack of budget.
- Individual institutes should do more to facilitate access to education for their staff.
- At educational events, learners want interaction with speakers and fellow participants, and there is a significant preference for practical learning modalities and face-to-face learning experiences.
- Despite problems with time and budget, online learning resources are not greatly used and do not seem to be particularly favoured by learners.
- Healthcare professionals are still under-informed about the valuable input patients can have in both research and healthcare.
The Summer School in Translation Cancer Research – which was performed the very first time in 2011 with FEBS - addressed both the issue of multidisciplinarity and the gaps between the cancer continuum’s parts. It reaches out to a broad range of course participants with different backgrounds all over Europe and beyond, and have since start-up been very well rated and highly appreciated by participants. The establishment of the EurocanPlatform Summer School in Translational Cancer Research as a popular, sustainable model of educational event, which responds to a previously unmet need in multidisciplinary, translational research education can be considered one of the principal successes to emerge from the Platform as a whole. The Summer School continues under the umbrella of Cancer Core Europe.
An objective of the EurocanPlatform was to create a common educational program. The TRYTRAC was an initiative within the platform that concerns startup of a new translational cancer research training program prospectively aimed for clinicians, to develop the next generation of cancer treatment, notably personalized cancer medicine. Cancer Core Europe has taken over the initiative and drives the development among the Cancer Core Europe centres.
The potential impact
This paragraph is divided into two. The first part concerns the different workpackages’ descriptions of the direct and/or indirect impacts of their output, followed by a second part with the impacts of the gathered EurocanPlatform’s work and activities.
I) WORKPACKAGES – Potential impact
WP2 - Prevention
WP2 has generated new knowledge for cancer prevention, which has made a significant impact on:
- promoting application of omics methodologies developed by EurocanPlatform partners to population-based cohorts and translational research involving the application of biomarkers for early detection, cancer risk stratification,
- providing some new basis (methods, infrastructure, knowledge) to facilitate identification of new carcinogens that may subsequently facilitate the implementation of strategies that limit carcinogenic exposure and cancer risk,
- promoting the use of cancer registries in translational research and research using population-based cancer registries,
- enabling the development of multidisciplinary studies on chemoprevention on colorectal cancer and breast cancer,
- preparing a long-term action plan to develop a sustainable infrastructure for prevention research in Europe (Cancer Prevention Europe coordination) with a funding commitment from six to eight leading institutions.
WP3 - Early detection
The activity of WP3 could significantly impact rationalization of care and cost reduction in terms of:
- possibility of a transition from tissue to liquid biopsy which is more practical, less invasive and cheaper.
- use ctDNA for early detection of relapse would avoid costly and ineffective diagnostic imaging (oklart).
- risk stratification and minimal residual disease detection in lung and breast settings, that could reduce the administration of inefficient therapies, leading to an economic advantage for the community.
- future expensive targeted therapies administration with more precision according to tumor molecular features detected in the tissue or in blood and/or in CTCs.
The outcome of this WP and its possible applications have been shared and discussed with patient advocate groups, and presented during large scientific conferences such as ASCO, SABCS, AACR and National/International meetings.
Moreover, a dedicated scientific event (a 2-day workshop on liquid biopsy) was organized, and tailored to specific groups of stakeholders such as clinicians, biomedical researchers, MD, PhDs, post-doc and PhD students.
WP4 - Kinome analyses to guide therapy choice
WP4 molecularly characterized a set of high-grade serous carcinoma using the most advanced genomic technologies, such as Next-Generation Sequencing, Reverse Phase Protein Assay and Low-coverage sequencing. The study identified a potential ongogenic mutation in the JAK3 gene, which, upon additional validation and functional characterization, could help in the selection of high-grade serous carcinoma and guide treatment decisions.
WP6 - Therapeutic strategies
Two main initiatives, EuroPDX and Cancer Core Europe, emerged during the EurocanPlatform project and aims to maintain the collaborative network built during the project time. Their objective is to consolidate the integrated view of EurocanPlatform partners on how new targeted drugs should be developed and lead the shift in the design, strategy and methodology of phase I and early phase II trials.
- The Cancer Core Europe consortium looks to pave the way for a multi-site European Cancer Institute that will drive the development of new treatments and earlier diagnoses for patients and more effective cancer prevention for Europe’s citizens. Cancer Core Europe has set up a number of Task Forces around critical topics, one being Clinical Trials, where a first trial, Basket of Baskets, is underway, sponsored by VHIO on behalf of Cancer Core Europe.
- The EuroPDX works to improve the efficiency of drug development in oncology. This is done through the use of preclinical models that more closely recapitulate the heterogeneity of human cancers and perform studies for genotype/response correlation on a population scale, to achieve scientific solidity.
WP7 - Mouse tumour models
The mouse models generated in this consortium are now extensively used to test a diversity of targeted therapies and combination therapies. In breast cancer WP7 have identified several drug resistance mechanisms that are also occurring in patients. New combination therapies have been tested in NSCLC and pancreatic cancer. These studies provide new rationales for the design of new drug combination therapies to be tested in patients.
WP9 - Bioinformatics / Integration of information for pathway control
As an outcome of WP9, we developed novel computational approaches for accurately detecting and characterizing cancer-associated genomic structural rearrangements (SRs) including a cloud-based framework, Butler (Rausch et al. Bioinformatics 2012). The Butler framework, which is used within the Pan-cancer analysis of whole genomes (PCAWG) project became the life science demonstrator project within the European open science cloud pilot study (http://eoscpilot.eu/) from January 2017.
- By applying these new approaches, we described yet undiscovered mechanisms how cancer develop including enhancer hijacking in adult solid tumors, chromothripsis in medulloblastoma, androgen-driven structural rearrangements in prostate cancer (Rausch et al. Cell 2012; Weischenfeldt et al. Cancer Cell 2013; Korbel & Campbell Cell 2013; Northcott et al. Nature 2014; Fischer et al. Nat Genet 2015; Weischenfeldt et al. Nat Genet 2017) and furthermore provide alternative treatment options for e.g. ALL which could provide a cure for patients suffering from this deadly disease.
- Used the ArrayExpress functional genomics archive (Kolesnikov et al. 2015, Nucleic Acids Research) and reprocessed in the EMBL-EBI’s Expression Atlas (Petryszak et al. 2016, Nucleic Acids Research) for disseminating relevant datasets.
WP10 - Biobanking
Activities of the biobanking group aid to improve the quality- and progress – of translational cancer research, which is of benefit for end users, the patients.
WP10 has produced a number of guidelines/recommendations, so called CEN TS, on standardisations regarding samples/biobanking material. The impact of the CEN TS publications is already seen in BBMRI-ERIC where the implementation has started in developing self-assessment tools for biobanks. SPIDIA4P is a new H2020 project, which started this year. It deals with further development of documents for CEN and bringing CEN documents to the ISO level, along with external quality assessment and self-assessment tools on the different categories of diagnostic samples. This project builds upon the two FP7 projects SPIDIA and EurocanPlatform experiences and continues the initiative to increase reproducibility of results.
The access rules stimulating cooperation have been disseminated to all participating biobanks and beyond, stimulating sample exchange in multi centre research projects.
The Win-Win situations on sharing hospital biobank material were published in Sci Transl Med. 2015 Jul 22;7(297):297fs31, where it is accessible to the translational researcher instead of the biobankers, where it is integrated in a comprehensive model for biobank access and governance where the researcher stays involved in the sample exchange decision process. This takes away an important inhibiting factor, the possibility of losing control over information from analyses of samples and clinical data.
WP10 was highly engaged in the discussions about the European privacy regulations, when its changes headed into a direction where the regulation was becoming too strict to allow work within the field of translational research. These regulations are now acceptable for translational research.
WP11 - Clinical Epidemiology
The results from our collaborative studies on implementation and variations of cancer treatment modalities have already prompted a lot of attention by other European cancer centres after presenting the preliminary reports in several international scientific meetings. Although many of the studied treatment modalities may have already gained broad acceptance by expert opinion based on results from randomised clinical trials (RCTs), information on uptake and dissemination of these methods across countries has generally been very sparse. Monitoring and evaluating the spread and impact of these therapeutic innovations may strongly enhance more timely and efficient translation into real practice across European countries. Such translational research based on observational data, i.e. clinical validation, fills the knowledge gap left by RCTs and provides real-world results regarding uptake of treatment modalities and associated outcomes of patients in different healthcare systems.
WP12 - Quality assessment, accreditation and metrics
WP12 in collaboration with European Academy of Cancer Sciences have developed a methodology to evaluate CCCs of Excellence to guarantee Centres to be of the highest calibre. For the patients this is a high standard quality assurance that will aid therapy to progress and bring opportunities of improved therapeutics.
Additionally this WP developed a set of indicators to measure the outcome of the translational research i.e. production and activity, on the platform in terms of scientific and societal value. This set of indicators have a focus on the outcome of research on patients or public health and link innovation and quality of care.
WP13 - Education and training
WP13 performed an inventory of educational events, which clearly showed the deficit of the translational cancer research topic. One successful action and outcome of the EurocanPlatform is the Summer School in Translational Cancer Research, an initiative that is being performed for the fifth time this autumn. Here, participants with different backgrounds ranging from e.g. basic researchers, clinicians, bioinformaticians etc from mainly Europe come together for a week to interact with the expertise of the whole cancer continuum. The knowledge and network that is created during the course, provides opportunity to interactions, which will highly benefit both the research process and progress, by improving the integration between different disciplines.
Two thematic and one special issues of Molecular oncology: “Personalized cancer medicine” (Mol Onc 6:2, 2012), “Mouse models of cancers: Essential tools for better therapies” (Mol Onc 7:2, 2013), and “Clinical trials for development of personalized cancer medicine” (Mol Onc 9:5, 2015) were produced which were provided as educational material for the Summer school.
WP14 - Communication and dissemination
During the course of the EurocanPlatform project we have developed, published and hosted a wide range of communication and dissemination tools, these include:
- Project website – 18,321 unique visitors
- 8 news stories published on ecancer.org – 12,168 reads
- 101 educational videos – 268,973 views; Hosted on: Ecancer.org , Eurocanplatform.eu , You tube
- 2 conference reports – 732 reads
- 1 editorial – 141 reads
- 1 special issue – 3,396 reads; Containing 7 separate articles
- 4 Educational meetings with approximately 400 attendees: EBCC Conference in September 2013; ECC Conference in September 2013; ECPC Annual General Assembly 2014; ECPC Annual General Assembly 2015
- Social media promotion: #EurocanPlatform hashtag used 48 times with 22,176 impressions and 114 engagements ; 42 Facebook posts with 349 likes
- 12 project newsletters
Total engagements: 326,656
ecancer has set up and continued to maintain a dedicated online platform for the EurocanPlatform project: http://eurocanplatform.eu/. The website includes an internal project intranet, which was used by the partners to improve communication and project management and platforms to facilitate instant access, tumour markers and clinical trials.
A public outreach meeting titled ‘Translational and tailored, but can we afford it?’ was held at the EBCC conference in September 2013, involving a number of European patient advocacy groups such as ECPC, KEFI and FAVO. An additional session titled ‘Translational research comes of age’ was held alongside the September 2013 ECCO in Amsterdam, co-chaired by Professor Ulrik Ringborg and Professor Julio Celis. Dr Peter Riegman of Erasmus MC gave updates on the project in general as well as specifically patient-aimed activities, such as the biobanking FAQs at the 2014 ECPC Annual General Assembly and this was followed up a year later with a talk by Professor Julio Celis on ‘What will EurocanPlatform mean to both patients and institutions’.
ecancer has not only posted regular news stories through its dedicated project website and created new video content on achievements in the project.
ecancer published both regular website news as well as newsletters throughout the project. The final newsletter summed up project progress with the final press release, the cancer prevention special issue as well as a project promotional video. Promotional videos were also created for initiatives coming out of the EurocanPlatform project: Cancer Core Europe and Cancer Prevention Europe.
Furthermore, there has been three press releases: at the start-up of the project, the Poseidon clinical trial and finally, the last Annual meeting in Brussels.
II) OVERVIEW – Potential impact
About 15 years ago, the former Commissioner for Research Philippe Busquin, with the support of the European Parliament, promoted the creation of the European Cancer Research Area (ECRA) in 2002 to address the fragmentation of European cancer research. Patients were not receiving the treatments and diagnostics that they rightly demanded, and there was an urgent need to create a single European strategy for cancer research (1). To identify solutions to the challenge, Commissioner Busquin supported the start of the Eurocan+Plus project in FP6, which produced the most extensive analysis of European cancer research to date (2). The project identified leading causes underlying fragmentation including the increasing complexity of cancer biology, the large diversity of cancer diseases, suboptimal translational cancer research, the dearth of critical mass, as well as the regulatory obstacles and lack of coordination for cross-border collaboration. The Eurocan+Plus project proposed the creation of a translational cancer research platform linking basic/preclinical research centres with Comprehensive Cancer Centres (CCCs), institutions where treatment and prevention integrate with research and education, and link research with the healthcare system. Following completion of the project, leading representatives from 16 participating cancer research centres signed the Stockholm Declaration (3), signalling their commitment to developing long-term institutional collaborations by sharing resources and creating a culture of sharing and coordination. This key event, together with the support of the European Cancer Organization (ECCO), policy makers, and the cancer community (1) paved the way to the funding of the EurocanPlatform, a Network of Excellence in FP7. At this stage, the central part of the EurocanPlatform project agenda was in place.
Main outcomes of the EurocanPlatform project
The EurocanPlatform project brought together 23 European cancer research centres and five major cancer organisations with the aim of structuring translational cancer research to innovate in prevention, early detection and therapeutics. The primary objectives were to support the development of personalized cancer medicine, based on the understanding of the biology underlying the disease(s), to stratify patients for treatment, and to identify high-risk individuals for prevention and early detection. To date, variable geometries have been established for collaborations within the areas of prevention, early detection, therapeutics, and outcomes research.
A main achievement of the EurocanPlatform Consortium has been the creation of Cancer Core Europe in 2014 (4, 5), a virtual patient-centred multidisciplinary shared infrastructure addressing the cancer care/research continuum in partnership among six leading EurocanPlatform cancer centres:
- Gustave Roussy Cancer Campus Grand Paris,
- Cambridge Cancer Center, Cambridge,
- The Netherlands Cancer Institute (NKI), Amsterdam,
- Karolinska Institutet (KI), Stockholm,
- The Vall d’Hebron Institute of Oncology (VHIO), Barcelona, and
- The German Cancer Center with its CCC the National Centre for Tumour Diseases (DKFZ-NCT), Heidelberg).
Cancer Core Europe was established utilizing a bottom-up approach, and in the spirit of the “Stockholm Declaration”, each of the centres allocated their own resources to incite cross-border collaboration. With a rotating leadership, Gustave Roussy has taken the lead with Alexander Eggermont as Chairman and Fabien Calvo as Chief Scientific Officer. On Feb 18, 2017, 5 of the centres established a legal entity, a French Association; the Karolinska Institutet awaits approval by the Government to be able to enter the legal structure as this is required by Swedish law.
Cancer Core Europe has a significant critical mass as it sees 60,000 new cancer patients a year, treats about 300,000 patients, has about 1,200,000 consultations, and more than 1,500 clinical trials are being conducted at the six centres (6). Together, the centres have the necessary infrastructures for advanced science-driven innovations, and being a legal structure, Cancer Core Europe is in a unique position to create stimulating environments where the strategic priorities of Commissioner Moedas (Open Science, Open Innovation and Open to the World, including Science Diplomacy), could develop and flourish. For sharing resources and coordination, six task forces with representatives from all centres were established: data sharing, molecular diagnostics, immune-oncology, imaging, clinical trials, and education and training.
Cancer Core Europe offers significant advantages regarding the implementation of complete bidirectional translational research, these include: long-term collaboration between CCCs to guarantee sustainability; a legal entity, prerequisite for “open science”; a quality assured cancer research environments to cover the complete cancer research continuum thanks to a Designation program for CCCs of Excellence (see below); addressing medical prevention options in a continuum with early treatment; supporting development of new tumour classifications based on deranged molecular pathways; combination treatments to target molecular pathways; structuring clinical effectiveness research for clinical validation and assessment of clinical utility; definition of evidence including quality of life assessment; health economics for cost-effectiveness; dissemination of innovations to clinical trials networks for further process towards clinical guidelines and adoption by the health care systems. Furthermore, Cancer Core Europe provides unique opportunities for more science-driven clinical trials in collaboration with the pharmaceutical industry.
Presently, there is a plan regarding a controlled expansion of the consortium by incorporating additional centres. In the long-term, the aim of the consortium is the creation of a sustainable “virtual multi-site European Cancer Institute (ECI), built on the most innovative CCCs, which will drive the development of new treatments and earlier diagnoses for patients, and more efficient cancer prevention for Europe’s citizens” (6). Work is continuously underway to ensure the sustainability of Cancer Core Europe.
The success of Cancer Core Europe in building a consortium for therapeutics, stimulated representatives of the geometry for prevention within EurocanPlatform to use the same strategy to create a similar parallel infrastructure. Accordingly, Chris Wild, from IARC, has led the initiative to establish Cancer Prevention Europe. An interim Steering Committee with Christopher Wild as chairman and David Forman as scientific officer has been created representing the following participants: Cancer Research UK; Danish Cancer Society Research Centre, Copenhagen; German Cancer Research Centre, Heidelberg; Imperial College, London; Karolinska Institutet, Stockholm; UK Therapeutic Cancer Prevention Network, Leicester, UK. A draft Consortium Agreement has been prepared and is currently being reviewed by the potential core partners. IARC has established a secretariat for Cancer Prevention Europe in Lyon, and a work programme is currently under development.
The Cancer Prevention Europe programme identifies obstacles and will offer solutions to increase the effectiveness of translational cancer research to innovate in prevention. Integrated and coherent strategies for primary, secondary and tertiary prevention are unmet needs, and the roles of CCCs and other prevention organisations must be clearly defined. Moreover, there is an urgent need to improve the connection between cancer biology and development of new prevention strategies. The two-way translational cancer research concept suggested by Christopher Wild – i.e. research in the boundary between pre-malignant and malignant lesions – is expected to stimulate both medical prevention and treatment of early invasive disease. Finally, the complexity of late translational research, being of another magnitude as therapeutic research, needs to be converted into practical goals to improve the implementation of prevention strategies. Cancer Prevention Europe intends to create effective collaborative networks and articulate prevention strategies that will make it attractive as an entity for funding by charities and EU programs.
By definition, CCCs integrate cancer care and prevention/early diagnosis with research and education aiming at innovation. European criteria and an accreditation methodology for CCCs have been developed by the Organisation of European Cancer Institutes, and there are also national initiatives to designate CCCs. The need to further boost high quality cancer research environments for translational research has triggered the development of a program to Designate CCCs of Excellence. Such a program has been established by EurocanPlatform in collaboration with the European Academy of Cancer Sciences (EACS), which acts as the designating body. Research environments will be evaluated for their excellence with regard to both available infrastructures as well as translational research activities that need to cover the continuum of internationally leading basic cancer research to practice changing investigator-initiated clinical trials. A Standing Committee within the EACS under the leadership of Anton Berns will analyse the first two CCCs with the support of international auditors in March this year.
Structuring translational cancer research requires the integration of basic/preclinical research, early detection and outcomes research. Bridges between preclinical and clinical research are being continuously built, and a good example is the preclinical research, involving Patient-Derived Tumour Xenografts that are linked to the POSEIDON breast cancer trial, an early clinical trial for metastatic breast cancer patients. Three of the former EurocanPlatform Partners / current Cancer Core Europe participants (Netherlands Cancer Institute, Vall d´Hebron Institute of Oncology, and Cambridge Cancer Centre) are executing this trial. Next generation clinical trials are on the agenda of Cancer Core Europe. Biomarker research for early detection has a role both in Cancer Core Europe (early invasive and metastatic disease), and Cancer Prevention Europe (premalignant and early invasive tumours). Outcome research is an important research component in both consortia and for Cancer Core Europe clinical effectiveness assessments to clinically validate innovations has a high priority.
Another important mission of the EurocanPlatform project has been Education activities focused on translational research and multidisciplinary/international collaborations. The fourth Summer School in translational cancer research was held in October 2016, and in the future, the School will be organised under the umbrella of Cancer Core Europe and the German Cancer Consortium. A program for the education of next generation of leaders has been outlined by Cancer Core Europe. This program will also be relevant for Cancer Prevention Europe as well as other CCCs. It is worth mentioning that Cancer Core Europe is being seen as an infrastructure that will facilitate training and mobility of researchers and clinicians. The latter will ensure that all countries in Europe - in particular, EU-13 countries - benefit from this development. Applying Science Diplomacy may prove instrumental in addressing this challenge.
Structuring translational cancer research for both therapeutics and prevention is expected to have a significant impact on the way in which science-driven innovations are implemented. An important next step will be to translate the innovations into evidence-based guidelines and to ensure that the health care systems and prevention organizations quality assure their activities. Achieving these objectives will require a pro-active and sustained effort of all stakeholders as well as a great deal of political creativeness and commitment at all levels of the EU institutional triangle of power (1). Also, continuous science policy support will be necessary to secure a balanced approach in order to further improve cancer research, cancer care, and cancer prevention with the aim of boosting social innovation, a top priority of the European Commission today. The Science Policy Committee of the EACS could play a significant role in this context by conducting the necessary analyses and delivering evidence-based advice to drive policy.
1. Celis, J.E and Pavalkis, D. Funding mechanisms: A case study on translational oncology in the era of open innovation, open science, and open to the world. In Europe´s future: Open science, open innovation and open to the world. European Commission, in press.
3. Ringborg, U., 2008. The Stockholm declaration. Mol. Oncol. 2, 10-11.4.
4. Celis, J.E. Ringborg, U., 2014. Cancer Core Europe: a first step towards a virtual cancer institute in Europe? Mol. Oncol. 8, 1161–1162.
5. Eggermont, A.M. Caldas, C., Ringborg, U., Medema, R. Tabernero, J, Wiestler, O., 2014. Cancer Core Europe: A consortium to address the cancer care-cancer research continuum challenge. Eur. J. Cancer. 50, 2745-2746
List of Websites:
Info contact: http://eurocanplatform.eu/contact
Public website: http://eurocanplatform.eu/about
Project Coordinator: Ulrik Ringborg, Ulrik.Ringborg@ki.se
Project Vice Coordinator: Rolf Lewensohn, Rolf.Lewensohn@ki.se
Project Manager: Christina von Gertten, Christina.von.Gertten@ki.se
Project Financial Manager: Evelyn Göransson, Evelyn.Goransson@ki.se
Grant agreement ID: 260791
1 January 2011
31 December 2016
€ 15 561 005,72
€ 11 998 454
Deliverables not available
Grant agreement ID: 260791
1 January 2011
31 December 2016
€ 15 561 005,72
€ 11 998 454
Grant agreement ID: 260791
1 January 2011
31 December 2016
€ 15 561 005,72
€ 11 998 454