The specific objectives of this funding opportunity are to stimulate new partnerships between researchers and clinicians and support original, high-quality projects, which have the potential for significant clinical impact on HTTC prognosis. The expected outcome of the call is to improve the efficacy of current diagnosis, prognosis and treatment of HTTC, through the development of novel personalized approaches based on a better understanding of the peculiarities of HTTC.

Current difficulties include the inadequacy of standard diagnostic tools or established early detection methods in the general population, but also the inefficacy of available treatment options, due to intrinsic resistance and/or ineffective drug delivery. In the context of translational cancer research, this call for proposals comprises three specific aims. Proposals will have to cover at least one of the undermentioned aims or sub-aims.

Aim 1) Identification/validation of novel early diagnostic approaches. Early detection and diagnosis (ED&D) research seeks to detect and diagnose consequential precancerous changes and cancer at the earliest possible point at which an effective intervention might be made, reducing the burden of late-stage disease. Any of the areas identified below can be eligible for funding:

• Identification and validation of novel biomarkers/signatures for HTTC, to better understand disease trajectory of very early/pre-cancerous lesions and help patient stratification in terms of risk, diagnosis/prognosis, response to treatment;
• Non-confirmatory clinical trials of ED&D technologies or approaches, in particular data and computation-driven approaches.

Proposals may include hypothesis-driven studies on a variety of biomarkers, e.g. structural, functional, molecular, genetic biomarkers; digital biomarkers are eligible only in combination with other bio-signatures. In all cases, a clear pathophysiological correlate and studies on human participants or tissue should be included in the proposal.

Aim 2) Identification/validation of novel therapeutic approaches. Although ED&D may significantly reduce the disease burden, HTTC are often characterised by an intrinsic resistance to available treatments. Therefore, it is of foremost importance to understand the biological processes that make these cancers “hard to treat”, and consequently to elaborate more effective therapeutic strategies, also to improve the patients’ quality of life. We welcome proposals aimed at:

• Identification and validation of novel therapeutical targets, based on better insights on resistance mechanisms, tumour heterogeneity, cellular plasticity, tumour microenvironment, immune responses, metastatic process, tumour dormancy. Novel targets should be evaluated in translational studies with regard to their impact on treatment efficacy and patient benefits. Any in-vitro model systems must closely relate to the human disease.
• Development of novel therapeutics/therapeutic approaches, through phase I and II clinical trials investigating combinations of available treatments, e.g. targeting multiple pathways, including immune/inflammatory, neoangiogenic and proliferative pathways, new therapeutics, new administration schemes, nutritional support, and other measures to maximise patient outcome and quality of life.

Aim 3) Development of novel drug delivery strategies. The overarching challenge associated with effective treatment of any cancer is to minimize undesired effects while maximizing therapeutic benefits. For HTTC two additional issues arise: (i) traditional targeted drug delivery strategies suffer from limited capacity of the delivery vehicles preventing sufficient drugs reaching the cancer site which restricts the efficacy of treatment; and (ii) to access the tumour the drug needs to cross endogenous barriers, such as the blood brain barrier and tissue stroma. Therefore, we welcome proposals that aim at developing novel drug delivery systems for HTTC by:

• achieving site-specific targeting; and/or
• controlling release rate.

Interdisciplinary approaches that combine polymer science and nanotechnology, pharmaceutics, bioconjugate chemistry, and molecular biology are particularly supported.

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

Proposals addressing one or more of the above challenges with spatial transcriptomic, single-cell/multi-omic approaches are strongly encouraged, as well as other innovative approaches (artificial intelligence, radiomics, etc.) or strong biomedical components (e.g. organoids, cancer vaccines, etc.). 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, 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; and,

•           Studies not compliant with the Commission Regulation (EU) No 651/2014 of 17 June 2014.

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 to the Call Text (see pp. 24-26):

• 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.

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 2022, 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.
• The maximum number of partners can be increased to 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 of the Call Text (see pp.14-15).
• 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 4, coming from 3 different countries).
• A wide inclusion of research teams from all the countries/regions participating in the call is encouraged, with a particular attention to research teams from Hungary, Latvia, and Slovakia, in order to strengthen the European translational cancer research area.
• 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 JTC2022 (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, please refer to  Annex 1 to the Call Text (pp. 19-21).
• 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,
  • Alliance Against Cancer (ACC), Italy; and,
  • Chief Scientist Office – Ministry of Health (CSO-MOH), Israel.

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.