Call for proposals co-funded by the European Commission on "Translational research on human tumour heterogeneity to overcome recurrence and resistance to therapy"

Call for proposals co-funded by the European Commission on "Translational research on human tumour heterogeneity to overcome recurrence and resistance to therapy"

The ERA-NET: Aligning national/regional translational cancer research programmes and activities (TRANSCAN-2) is the continuation of the ERA-NET on Translational Cancer Research (TRANSCAN) and has the goal of coordinating national and regional funding programmes for research in the area of translational cancer research. The specific challenge is to promote a transnational collaborative approach between scientific teams in demanding areas of translational cancer research while avoiding the duplication of efforts and ensuring a more efficient use of available resources, to produce significant results of higher quality and impact, and share data and infrastructures.

Along this line the TRANSCAN-2 consortium launches its first Joint Transnational Call for research proposals (JTC 2014) co-funded by the European Commission on the following topic:

"Translational research on human tumour heterogeneity to overcome recurrence and resistance to therapy" 

The following funding organizations have agreed to participate in the EC co-funded JTC 2014:

·  Austrian Science Fund (FWF), Austria
·  Fund for Scientific Research (FNRS), Belgium
·  Research Foundation - Flanders (FWO), Belgium
·  Estonian Research Council (ETAg), Estonia
·  National Cancer Institute (INCa), France
·  ARC French Foundation for Cancer Research (ARC Foundation), France
·  Federal Ministry of Education and Research (BMBF), Germany
·  General Secretariat for Research and Technology, Ministry of Education and Religious Affairs (GSRT), Greece
·  The Chief Scientist Office of the Ministry of Health (CSO-MOH), Israel
·  Alliance Against Cancer (ACC), Italy
·  Ministry of Education, Universities and Research (MIUR), Italy
·  Ministry of Health (MoH), Italy
·  Latvian Academy of Sciences (LAS), Latvia
·  Dutch Cancer Society (DCS), Netherlands
·  Netherlands Organisation for Health Research and Development (ZonMw), Netherlands
·  The Research Council of Norway (RCN), Norway
·  Norwegian Cancer Society (NCS), Norway
·  National Centre for Research and Development (NCBR), Poland
·  Foundation for Science and Technology (FCT), Portugal
·  Slovak Academy of Sciences (SAS), Slovakia
·  Ministry of Education, Science and Sport (MIZS), Slovenia
·  The Foundation for the support of the Applied Scientific Research and Technology in Asturias (FICYT), Spain
·  Institute of Health Carlos III (ISCIII), Spain
·  Ministry of Science and Technology (MoST), Taiwan
·  The Scientific and Technological Research Council of Turkey (TÜBITAK), Turkey

The Italian Ministry of Health (Ministero della Salute, MoH) and the National Institute of Health (Istituto Superiore di Sanità, ISS) will act as Joint Call Secretariat (JCS) to coordinate the application and selection process of JTC 2014.

Cancer diagnosis and treatment has improved significantly over the last decade, with a wide range of therapeutic strategies for oncologists to pick up. Despite this, some tumours remain incurable and response to treatment is often of limited duration. The tumour heterogeneity within a given patient, either within the primary tumour or between the primary tumour and the metastases, contributes to treatment failure:
· Prognosis evaluation may be confounded by tumour heterogeneity issues, leading to inadequate therapeutic strategies and ultimately to recurrence.
· Treatment may be ineffective to target some specific sub-clones present in the primary tumour or in the metastases.
· Resistant clones emerge during treatment leading to the inefficacy of treatment and progressive disease.
Thus, tumour heterogeneity is a major challenge to address for the next decade by developing sampling and analysis methods able to record these phenomena, by deciphering the mechanisms underlying intra-tumour heterogeneity and its dynamic process and by assessing its impact on the efficiency of therapeutic strategies. Approaches should allow identifying appropriate targets for tumour monitoring, drug targeting, and to develop robust predictive biomarkers in order to improve treatment outcome and to limit the development or overcome drug resistance.
Tumour complexity is a result of continuous crosstalk between the tumour cells and the environment. Evaluating tumours as complex bodies and not simply as a mass of tumour cells becomes crucial, highlighting the needs of developing integrated approaches. Multi-omics/system biology approaches provide unique opportunities for elucidating intra-tumour heterogeneity by strategies combining technologies (genomic, epigenomic, cellular, microbiotic, exposome, metabolomic, nanotechnology, imaging, etc.), resources and data. Research groups should nfind the best way to share, integrate and combine tools and data in order to optimize their use and to obtain robust results directly transferable to the clinic.
To this end TRANSCAN-2 partners have agreed to focus their first call for proposals on "Translational research on human tumour heterogeneity to overcome recurrence and resistance to therapy". TRANSCAN-2 aims at promoting highly innovative and ambitious collaborative projects in translational cancer research at a European level, and believes that it is timely relevant to foster the translation new knowledge on tumour heterogeneity into clinical practices.
The expected impact of the call is to improve the efficacy of personalized treatment of cancer patients through the development of new tools and targeted therapeutic strategies, based on a better understanding of intra-tumour heterogeneity mechanisms and of their impact on the disease course.

“Human tumour heterogeneity” is defined in this call as heterogeneity within the tumour or between the primary tumour and metastatic sites within a same patient. In the context of Translational Research, this topic will comprise three specific aims which concur to the possible clinical applications. Proposals will have to cover at least one of the specific areas listed under each aim below. Projects should be built from a solid and established hypothesis and should be relevant with regards to the possible improvements in clinical practices.
Aim 1: Development and validation of methods to investigate human tumour heterogeneity (including heterogeneity between the primary tumour and the metastatic sites)
Sampling methods alternative to single biopsy (liquid biopsy, single cell analyses, imaging, etc.) for overcoming tumour sampling bias;
Methods for assessing tumour heterogeneity, within either the primary tumour or the metastases;
Methods for tracking tumour evolution along the disease course using minimally- or non-invasive techniques.
Aim 2: Studies on human tumour heterogeneity in order to guide therapeutic intervention and identify new therapeutic targets
Evaluation of the impact of tumour heterogeneity on treatment efficacy and patient outcome (clinical utility of driver/passengers mutations detection, clinical utility of the minor sub-clones identification, clinical utility of the differences in molecular alterations between primary tumour and metastases);
Development of assays measuring the level of tumour heterogeneity that predicts treatment inefficacy and tumour recurrence;
Development of assays that define the contribution of tumour heterogeneity to resistance mechanisms and identify new therapeutic targets.
Aim 3: Development of new precision therapeutic strategies that may prevent human tumour recurrence or resistance to therapy by counteracting tumour heterogeneity
Evaluation of treatments (combinations, new strategies, administration scheme) targeting multiple sub-clonal somatic events or preventing resistant sub-clones to emerge.

There will be a two-stage submission procedure for joint applications: pre-proposals and full proposals. Both types of proposals must be written in English and must be submitted electronically to the JCS by the coordinator. Pre-proposals and full proposals should strictly follow the rules described in the Guidelines for Applicants. To apply, please use the appropriate Pre-proposal Application Form.
 Pre-proposals must be submitted exclusively through the electronic submission system at CBIM- Italy by the deadline of 16 March 2015 at 16:00 (Central European Time, CET). All proposals will be subject to a peer-review and a joint decision process of the funding organisations involved.
Successful applicants from the pre-proposal stage will be invited to submit their full proposals not later than 7 July 2015 at 16:00 (Central European Summer Time, CEST). Please note that full proposals will only be accepted from applicants explicitly invited by the JCS.
Applicants may request funding for individual grants according to national/regional rules. Please note that, for applicants from some countries/regions, it may be necessary to submit their proposals and/or other information not only to the JCS, but also to their relevant national/regional funding organisations. Therefore, applicants are strongly advised to check with their national/regional funding organisations for more details (see Annex 1. Contact information of the National/Regional Funding Organisations, Guidelines for Applicants).
Based on the time required for the approval process for granting funds to the respective national/regional research groups, individual projects of a research consortium are expected to start in April 2015.

Publication of the JTC 2014: 15 January 2015
Opening of electronic submission system for pre-proposals: 16 February 2015
Deadline for electronic pre-proposals submission: 16 March 2015
Opening of electronic submission system for full proposals: 26 May 2015
Deadline for electronic full proposals submission: 7 July 2015
Communication of final evaluation result and funding decision: October 2015
Start of funded research projects: April 2016