Call for research proposals on “Novel translational approaches to tackle the challenges of hard-to-treat cancers from early diagnosis to therapy”

Call for research proposals on “Novel translational approaches to tackle the challenges of hard-to-treat cancers from early diagnosis to therapy”

TRANSCAN-3 partners have agreed to focus their second Joint Transnational Call for proposals (JTC 2022) on:

“Novel translational approaches to tackle the challenges of hard-to-treat cancers from early diagnosis to therapy”

The following national/regional funding organisations have agreed to participate in the JTC 2022:

  • Austrian Science Fund (FWF), Austria
  • Research Foundation - Flanders (FWO), Belgium, Flanders
  • Fund for Scientific Research - FNRS (F.R.S.-FNRS), Belgium, French speaking community
  • Estonian Research Council (ETAg), Estonia
  • French National Cancer Institute (INCa), France
  • ARC French Foundation for Cancer Research (ARC Foundation), 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
  • Alliance Against Cancer (ACC), 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
  • Research Council of Norway (RCN), Norway
  • Norwegian Cancer Society (NCS), 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
  • Ministry of Science and Technology (MoST), Taiwan

The call is published simultaneously by the participating funding organisations in their respective countries and on the TRANSCAN website.

Interested researchers and/or research teams are advised to prepare and make the necessary contacts and arrangements towards preparing applications.

Alliance Against Cancer acts as Joint Call Secretariat (JCS) to coordinate the application and selection process of JTC 2022 (see contact details on the Call Text frontpage).

For full details of the call motivation, topic, eligibility criteria, etc., please consult the following related documents: Call Text, Guidelines for Applicants, National contact points and pre-proposal application form.

Motivation

The EU has been working to tackle cancer for decades and its strategic actions, for example on tobacco control and protection from hazardous substances, have saved and prolonged lives. Along with incidence, mortality, and prevalence, survival is a key indicator for cancer surveillance: it allows to assess the overall improvement in cancer patients’ prognosis, resulting both from initiatives implemented to diagnose cancers at earlier stages or to improve cancer care, and from therapeutic progresses. Survival rate for most cancers has doubled over the past 40 years, with 50% of patients surviving to 10 years or longer. However, progress has not advanced equally for all forms of cancer. According to the most authoritative cancer epidemiology registries in the Western world (e.g., the NIH Surveillance, Epidemiology, and End Results (SEER) Program, https://seer.cancer.gov or the IARC Cancer Survival in High-Income Countries (SURVMARK-2) project, https://gco.iarc.fr/survival/survmark), survival for some types of cancer is lagging behind, due to the lack of successful treatment. For some Hard-To-Treat Cancers (HTTC), the 5-year survival rate is still lower than 35% and little or no improvement has occurred in the past decades; these include tumours arising in the oesophagus, liver and annexes, pancreas, lung/pleura, and brain.

The causes of therapeutic failure can be multiple: late detection due to lack of advanced diagnostics, absence of appropriate biomarkers and/or targeted approaches, tumour heterogeneity, acquired drug resistance, problematic drug development due to the rarity of some tumour types, as well as tumour- and site-specific hurdles. For example, glioblastoma has ill-defined boundaries, which complicates surgical removal, while the blood-brain barrier hampers drug penetration into the tumour. Drug penetration is also problematic in mesothelioma and pancreatic tumours, due to their fibrous outer layers. Oesophageal cancer is characterised by early lymph node metastases, due to the anatomy of the mucosa, and multifocal lesions, which increases heterogeneity.

Tackling the manifold challenges presented by HTTC is a key priority in the translational cancer research arena, very relevant to the European Commission’s Cancer Mission and the Europe’s Beating Cancer Plan, which together aim to prevent cancer and to ensure a high quality of life for cancer patients through action on crucial areas such as early detection and diagnosis, treatment and follow-up. In addition, during the European Meetings of the French National Cancer Institute (INCa) held on February 3rd and 4th 2022, European stakeholders gathered to propose concrete actions building on the objectives of Europe’s Beating Cancer Plan and the Horizon Europe Cancer Mission. In this context, poor prognosis cancer was identified as one of the five priorities in the fight against cancer which can most benefit from increased European cooperation and coordinated actions.

Against this background, it appears essential to develop translational research at European level and beyond, to build new paradigms that could radically transform the prognosis of these cancers. TRANSCAN-3 aims at promoting highly innovative and ambitious collaborative projects in translational cancer research at European and international level, and considers that, based on the previous grounds, it is timely and relevant to foster the translation of a better understanding of HTTC into clinical practices.

Aims of the Call

Proposals must be centred on one or more of the HTTC subtypes characterised by very poor prognosis (5-year survival rate<25%) and for which survival has not improved significantly over the last decades, which are listed in the table below: 

 

5-year survival rate (2017)

Average absolute change 2006-2017

Glioblastoma

5.7%

0.1

Pancreas

10.9%

0.6

Pleural mesothelioma

11.5%

0.3

Gallbladder

19.4%

0.4

Oesophagus

19.9%

0.4

Liver and bile ducts

20.3%

0.7

Lung/bronchus

21.7%

0.5

Source: https://seer.cancer.gov

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.

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 2022.

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): 1) exchanges/mobility of investigators (especially young investigators) between teams and countries participating in the project, 2) short term training of scientists, operational staff, etc., 3) training through technical workshops dedicated to relevant aspects of the scientific work planned in the project, 4) short training (one or few weeks) of several partner teams by one expert, etc. Activities related to the dissemination of results such as hosting a symposium, conferences etc. are out of the scope of this capacity building component.

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 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.

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

Call Timeline

23 May 2022

Publication of the call

6 June 2022 at 16:00 (CEST)

Opening of the on-line submission system for pre-proposals

18 July 2022 at 12:00 (CEST)

Deadline for pre-proposal submission

3 November 2022

Communication of the results of the pre-proposal assessment and invitation for full-proposal stage

17 November 2022

Opening of the submission system for full proposals

15 December 2022 at 12:00 (CET)

Deadline for full-proposal submission

Expected for April 2023

Communication of the funding decisions to the applicants

September 2023

Expected project start (also subject to regional/national procedures)