Project description
A dual-action targeted therapy for triple-negative breast cancer
Triple-negative breast cancer is one of the most aggressive and difficult-to-treat cancer subtypes, with limited therapeutic options and poor survival rates. A protein called fibroblast activation protein is highly expressed in the tumour microenvironment but is largely absent from healthy tissue, making it an attractive therapeutic target. With the support of the Marie Skłodowska-Curie Actions programme, the BiFAP project aims to develop a single platform that combines chemotherapy and radionuclide therapy. To achieve this dual-targeting strategy, researchers propose to design targeted conjugates based on novel small molecules with exceptionally long tumour residence. The approach will be validated in organoid models and preclinical mouse studies, hoping to achieve enhanced tumour selectivity and reduced toxic side effects.
Objective
Triple-negative breast cancer (TNBC) remains one of the most aggressive subtypes of breast cancer, with limited therapeutic options and a poor prognosis. To offer dearly needed new treatment perspectives, we want to target fibroblast activation protein (FAP), a protease that is highly expressed on cancer-associated fibroblasts (CAFs) in tumors but negligible in most healthy tissue. Building on this rationale, the host institution has pioneered novel ketoFAPIs, small-molecule FAP inhibitors with exceptionally long tumor residence times, providing a unique opportunity to design advanced drug delivery platforms.
This project will exploit the unique properties of ketoFAPIs to design bimodal conjugates that combine chemotherapy and radionuclide therapy in a single, tumor-targeted platform. These conjugates will integrate: (i) a ketoFAPI as the primary targeting moiety, (ii) a DOTAGA chelator for radionuclide labeling, and (iii) a cleavable linker for selective intratumoral release of potent chemotherapeutics such as MMAE or SN-38. To further enhance tumor selectivity and reduce bone marrow toxicity, a dual-targeting strategy will be pursued by adding folic acid as a second tumor-binding ligand. The project is structured into three objectives: 1) synthesis and characterization of Type I and II conjugates, 2) in vitro validation of efficacy and selectivity in TNBC organoid models, 3) in vivo evaluation of biodistribution, tumor uptake, and bone marrow safety in TNBC mouse models.
By integrating long-residence FAP targeting with dual-modality therapy and dual-ligand selectivity, this research introduces a first-in-class therapeutic strategy for TNBC. Expected outcomes are optimized conjugates with enhanced tumor selectivity, reduced hematological toxicity, and improved therapeutic potential. Aligned with the EU’s Beating Cancer Plan, this project directly addresses the need for innovative, tumor-targeted therapies to improve cancer patient survival and quality of life.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences chemical sciences nuclear chemistry radiation chemistry
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
2000 Antwerpen
Belgium
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.