TRANSCAN-3 launches its third Joint Transnational Call for research proposals (JTC 2023) on the following topic:

“Translational research on cancer epigenetics”

The following national/regional funding organisations have agreed to participate in the JTC 2023:

• Austrian Science Fund (FWF), Austria
• Fund for Scientific Research - FNRS (F.R.S.-FNRS), Belgium, French speaking community
• Canadian Institutes of Health Research (CIHR), Canada
• Estonian Research Council (ETAg), Estonia
• ARC French Foundation for Cancer Research (ARC Foundation), France
• French National Cancer Institute (INCa), France
• Federal Ministry of Education and Research (BMBF), Germany
• National Research, Development and Innovation Office (NKFIH), Hungary
• Health Research Board (HRB), Ireland
• The Chief Scientist Office of the Ministry of Health (CSO-MOH), Israel
• Ministry of Health (IT-MOH), Italy
• Tuscany Region (TuscReg), Tuscany, Italy
• Fondazione Regionale per la Ricerca Biomedica (FRRB), Lombardy, Italy
• Latvian Council of Science (LCS), Latvia
• National Research Fund (FNR), Luxembourg
• Norwegian Cancer Society (NCS), Norway
• Research Council of Norway (RCN), Norway
• National Centre for Research and Development (NCBR), Poland
• Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI), Romania
• Slovak Academy of Sciences (SAS), Slovakia
• National Institute of Health Carlos III (ISCIII), Spain
• The Scientific Foundation of the Spanish Association Against Cancer (FCAECC), Spain
• National Science and Technology Council (NSTC), Taiwan
• The Scientific and Technological Research Council of Türkiye (TÜBITAK), Türkiye

The French National Cancer Institute (INCa) will act as Joint Call Secretariat (JCS) and will be responsible of the application and selection process of JTC 2023.

Motivation

In the last decades the understanding of the molecular mechanisms responsible for cancer development and progression has significantly improved. In particular, a lot of progress has been made regarding the genetics of cancer that has led to the discovery and implementation into the clinic of numerous treatments as well as many biomarkers to improve screening, diagnosis and prognosis of cancers, leading to an increase in survival and improvement in the quality of life of cancer patients.

Despite these significant advancements, there is still much to be learned about cancers research. More recently, epigenetics, the study of changes in gene expression without alterations in the DNA sequence, has emerged as an important area of investigation. The epigenetic research, driven by technological progress like high-throughput sequencing technology, has been developing rapidly. The improvement of knowledge of the chromatin structure and its accessibility along with the mechanisms of histone modifications has revealed the important role of epigenetic modifications in the gene expression. During development, the establishment of the epigenetic program is particularly important and its stability essential for the maintenance of the functions of each cell type. Alterations in epigenetic modifications are associated with several pathologies and have been particularly highlighted in cancers. It is commonly accepted now that cancers are as much epigenetic diseases as genetic ones. It remains to be understood to what extent these epigenetic alterations influence the development of a cancer and what their importance in tumour growth is.

Epigenetic changes can be observed between healthy and cancerous cells. Large-scale cancer epi/genome sequencing efforts have currently revealed a very large number of epigenetic marks and genetic alterations in cancer cells and tissues. They may have clinical utility as potential tumour biomarkers to help identify specific cells and target the cell of origin of a given tumour or classify tumour type. Epigenetics thus represents an important tool for the improvement of early detection and the prediction of the disease. Epigenetics and epigenomics therefore have significant potential for clinical application as they can help clinicians diagnose certain types of tumours and could help determine the efficacy of treatments.

The treatment targeting epigenetics is becoming an attractive and promising strategy for anticancer therapy. Indeed, unlike genetic alterations, which are irreversible, epigenetic modifications are reversible. This field of research thus offers great opportunity for new therapeutic approaches and has paved the way for the development of new therapeutic compounds, so-called epidrugs. Some new drugs directed at epigenetic modulators have already been developed and are available.

However, apart from a few cases, the clinical applications of epidrugs, alone or in combination with radiotherapy, chemotherapy or immunotherapy, are still far from common practice, particularly for solid tumours. It is therefore necessary to translate the fundamental knowledge of this emerging field into concrete clinical applications.

Aims of the Call

The expected outcome of the call is to improve the efficacy of current detection, diagnosis, prognosis and treatment of cancers, through the development of novel approaches based on a better understanding of cancer epigenetics. The specific objectives of this funding opportunity are to stimulate new partnerships between researchers and clinicians and support original, high-quality projects, with significant clinical impact.

In the context of translational research, this topic will comprise two general aims, each with several aims, which concur to the possible clinical applications. Proposals should cover one or several of the specific aims listed below and should be built from a sound hypothesis. Particular attention should be given to gender balance inclusion in order to intercept sex/gender differences and to consider the role of these differences in the addressed questions.

Aim 1) The role of epigenetics in cancer initiation and progression. These studies may aim to validate novel epigenetics-based biomarkers to improve detection, diagnosis, prognosis of cancers or response to therapies (using recently developed innovative approaches, multiomic approaches, single-cell analysis, patient-derived organoids, patient-derived xenografts, tumour samples collected from retrospective and/or prospective cohorts of patients or clinical trials).

• Specific aim 1.1: To understand cancer initiation and progression by characterisation of the epigenetic landscape.
• Specific aim 1.2: To define epigenetic features of cells in the tumour microenvironment that may promote tumour progression (e.g., immune cells, vascular cells, microbiota).
• Specific aim 1.3: To study the role of epigenetic modifications as predictors of cell persistence or treatment resistance.
• Specific aim 1.4: To validate epigenetic markers useful to improve early detection and diagnosis by exploring the correlation between epigenetics and clinical cancer manifestation.

Aim 2) Validation of new epigenetics-based therapeutic strategies to limit cancer progression, prevent relapse/recurrence or increase the efficiency or reduce toxicity of existing anti-cancer therapies.

• Specific aim 2.1: To validate novel therapeutic targets (novel targets should be evaluated in translational studies with regard to their impact on treatment efficacy, safety and patient reported outcomes).
• Specific aim 2.2: To study the potential use of epigenetic modulators to overcome resistance to anti-cancer therapies.
• Specific aim 2.3: To develop novel epidrugs/therapeutic approaches, through phase I and II clinical trials (investigating combinations of available treatments, new therapeutics, new administration schemes, etc.) to improve safety and efficacy of treatments (objective responses; patient reported outcomes regarding morbidity and quality of life; …).
• Specific aim 2.4: To develop novel theranostic approaches involving epigenetics of cancer. Approaches combining diagnostic (imaging technics) and targeted treatment to detect cancer cells and assess treatment efficacy (radionuclide, radiopharmaceuticals, nanoparticles, nanomaterial, …).

An essential pre-requisite for all proposals is the clinical relevance of the planned work.

We particularly welcome applications that propose novel interdisciplinary approaches from relevant fields of engineering, informatics, physics in addition to biology and medicine, provided that they are mindful of potential clinical need, patient and population impact.

The following types of research projects are excluded from the call:

•  Analysis of preclinical models limited to cell lines and animal models;
•  Phase III and IV clinical trials;
•  Studies not compliant with the COMMISSION REGULATION (EC) No 800/2008 (http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:214:0003:0047:en:PDF), with specific reference to the articles 30, 31, 32, and 33. For full reference, please see also the COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS dated 20.12.2011 (http://ec.europa.eu/services_general_interest/docs/comm_quality_framework_en.pdf);
• Studies not compliant with the Commission Regulation (EU) No 651/2014 of 17 June 2014 http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:2014:187:FULL&from=EN.

Capacity building activities

Translational research has the ambition to remove barriers to multidisciplinary and multi-professional collaboration. It is envisioned that clinicians, researchers and operational staff from various sectors (academia, industry, regulatory bodies) will effectively work together to expedite the translation of scientific discoveries to clinical application and to more rapidly fuel research directions with observational or clinical findings. In fact, the complexity of the process requires, at the individual and collective levels, the creation of translational medicine research interfaces/infrastructures. To reach that goal, TRANSCAN-3 supports capacity building activities to promote the formation and upgrading of multidisciplinary teams in an integrated process: i) exchange/mobility of individual researchers/professionals in order to bring new expertise to an existing multidisciplinary translational team; and/or ii) recruitment of individual researchers/professionals by a translational research team in order to cover expertise and “know-how” unavailable in the existing team. These types of activities, when present, will be supported within the projects, which will be selected for funding under TRANSCAN-3 JTC 2023.

Thus, applicants may add an additional part to cover these activities (eventually with an associated separate budget, in compliance with the rules of the respective national/regional funding organisations). Capacity building activities have to be fully coherent with the objectives of the research project, and aimed at strengthening the ability of participating team(s) to perform the work detailed in the project plan as well as to improve, in the long term, the quality and potential of the translational research performed by the team(s). Depending on the project these activities could be (the following examples are indicative only, and neither exhaustive nor prescriptive): exchanges/mobility of investigators (especially young investigators) between teams and countries participating in the project; short term training of scientists, operational staff, etc.; training through technical workshops dedicated to relevant aspects of the scientific work planned in the project; short training (one or few weeks) of several partner teams by one expert. Activities related to the dissemination of results such as hosting a symposium, conferences etc. are out of the scope of this capacity building component.

Application: Eligibility criteria

Joint transnational research proposals may be submitted by applicants belonging to one of the following categories depending on national/regional eligibility rules as specified in Annex 3 of the Call Text:

Academic research groups (from universities or other higher education or research institutions).

Clinical/public health sector research groups (from hospitals/public health and/or other health care settings and health organisations).

Enterprise's research groups (depending on national/regional eligibility rules), with particular emphasis on small and medium-sized enterprises.

The applicants are subject to eligibility criteria of national/regional funding organisations (see “Guidelines for applicants”) and are advised to contact their respective national/regional contact points (see Annex 1 of the Call Text).

Please note that non-compliance with the eligibility rules detailed below will lead to the rejection of the entire proposal without further review.

Only transnational projects will be funded.

Applications will be submitted by the coordinator. The coordinator and each of the individual project partners (representing research groups) will be funded by the funding organisation from their country/region that is participating in the TRANSCAN-3 JTC 2023, and are therefore subject to national/regional eligibility rules.

Each research consortium must involve a minimum of three (3) and a maximum of six (6) partners (comprising the project coordinator) eligible for funding, coming from different countries whose funders participate in the call.

In order to strengthen the European translational cancer research area, a wide inclusion of research teams from all the countries/regions participating in the call is encouraged, therefore the maximum number of partners can be increased up to seven (7) if they include one partner from the following participating countries: Hungary, Latvia, Slovakia and Turkey.

The maximum number of partners may also be increased to seven (7) in the full proposal stage as a consequence of the widening process aimed at including one team from underrepresented countries/regions, as detailed in Section 10.

The partners must be from at least three (3) different countries participating in the call. In addition, a consortium must not involve more than two (2) research groups from the same country (in such cases the minimum number of groups must be four (4), coming from three (3) different countries).

Each consortium is represented by a coordinator responsible for the scientific management (such as controlling, reporting, intellectual property rights issues, etc.) and for all the communications with the JCS.

Partners not eligible for funding by one of the organisations participating in the JTC2023 (e.g. from non-funding countries or not fundable according to the regional/national regulations of the participating funding organisations) may participate in projects provided that they demonstrate, with the full-proposal submission, that their economic and human resources have already been secured and will be available at the start of the project. No more than one partner with its own funding is allowed in consortia with at least three partners eligible for funding. Partners with their own funding must be comprised in the maximum number of six partners.

Applicants should refer to the annexes of the document “Guidelines for Applicants” containing all the specific national/regional eligibility criteria and should contact their respective national/regional funding organisation contact points for additional clarification (see Call Text:  Annex 1. Contact information of the national/regional funding organisations).

Please note that an eligibility check before the pre-proposal submission is mandatory for:

Ministry of Health (IT-MOH), Italy;

Fondazione Regionale per la Ricerca Biomedica (FRRB), Lombardy, Italy;

Tuscany Region (TuscReg), Italy;

Chief Scientist Office - Ministry of Health (CSO-MOH), Israel;

National Institute of Health Carlos III (ISCIII) and The Scientific Foundation of the Spanish Association Against Cancer (FCAECC); Spain.  

Each consortium must involve at least one basic or pre-clinical research team and one clinical team. It is also recommended to include an expert team in methodology, biostatistics or bioinformatics, depending on the type of work planned. The consortium may also involve other teams with specialised skills and know-how (biobanks, model systems, technological platforms, etc.) or expertise (epidemiology and molecular epidemiology, early phase clinical trials, public health, ELSI, etc.). The consortium should have sufficient critical mass to achieve ambitious scientific, technological and medical goals and, along with the particular contribution of each research team, should clearly demonstrate its transnational added value. The translational nature of the research results is the key goal of TRANSCAN-3, therefore the consortium should also clearly demonstrate a knowledge transfer towards clinical, public health and/or industrial applications.

The duration of the projects shall not exceed three (3) years. 

In case of interest in finding partners to the consortium, it is recommended to use the Partner Search Tool - Partfinder, provided by the National Centre for Research and Development (NCBR) on the website https://partfinder.ncbr.gov.pl. The usage of the aforementioned tool is voluntary and free of charge.[1]

Timeline of the Call

Submission of joint proposals

TRANSCAN-3 JTC 2023 will be implemented through a two-stage submission procedure: pre-proposals and full proposals. Both pre- and full proposals must be written in English and submitted to the JCS by the coordinator through the PT-Outline Electronic Submission System exclusively.

In preparing the proposals, applicants must strictly follow the rules described in this call text and in the document entitled “Guidelines for Applicants”, and use the application forms available on the TRANSCAN website (http://www.transcan.eu/) and on the electronic submission system. Applicants should take note of individual national/regional rules, and contact their national/regional contact points for specific questions.

The pre-proposals must be submitted to the electronic submission system no later than the 21^st July 2023, at 12:00 (Central European Summer Time, CEST). The information relating to the selected pre-proposal will be communicated to the coordinators on the 27^th October 2023.

The information provided in the pre-proposal application is binding for the entire application process. Thus, any substantial changes between the pre-proposal and the full proposal (e.g. composition of the consortia, objectives of the project, etc.) must be communicated in advance to the JCS with detailed justification and will only be allowed by the CSC under exceptional circumstances.

The invited full proposals will have to be submitted to the electronic submission system not later than the 15^th December 2023 at 12:00 (Central European Time, CET). Please note that full proposals will only be accepted from applicants explicitly invited by the JCS to submit.

The decision on the results of the full proposal evaluation meeting will be communicated to all (successful and unsuccessful) coordinators in May 2024. Coordinators will receive a summary of the full proposal evaluation conclusions in due time.