Objective
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options and poorer survival. PARP inhibitors (PARPi) are the only approved targeted therapy but are restricted to ~15% of patients with homologous recombination deficiencies (HRD), underscoring the urgent need for functional biomarkers to expand their clinical reach.
Our recent work points to nuclear metabolism as a regulator of genome function and therapy response. We identified that inosine monophosphate dehydrogenase 2 (IMPDH2), a purine biosynthesis enzyme, relocates to chromatin during DNA damage, where it interacts with PARP1 and consumes nuclear NAD⁺. In TNBC, we found that nuclear IMPDH2 is enriched and correlates with tumour aggressiveness, and that its activity modulates sensitivity to PARPi, supporting its potential as a predictive biomarker in a spatially defined tumour context.
NuMAP-TNBC will test the hypothesis that nuclear IMPDH2 can guide PARPi response beyond HRD through four objectives:
(1) Define molecular programmes linked to nuclear IMPDH2 by combining spatial transcriptomics and protein mapping in patient-derived xenograft tumours.
(2) Characterise the distribution of nuclear IMPDH2 in patient breast cancer tissue and determine how it associates with cell types of the tumour microenvironment.
(3) Build an integrated spatial atlas of nuclear IMPDH2 that connects protein features, transcriptional states, and cellular neighbourhoods to uncover biomarker signatures.
(4) Develop and validate predictive models of therapy response based on nuclear IMPDH2, enabling patient stratification for PARPi treatment beyond HRD status.
By bridging nuclear metabolism, spatial biology, and computational pathology, NuMAP-TNBC will provide mechanistic insight into chromatin-associated metabolic enzymes and deliver a practical, spatially resolved biomarker strategy. Its impact will be to expand PARPi eligibility and improve outcomes for patients with TNBC.
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 genetics DNA
- medical and health sciences clinical medicine oncology breast cancer
- medical and health sciences basic medicine pathology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
You need to log in or register to use this function
Keywords
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
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.
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
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.
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
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
See all projects funded under this callCoordinator
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.
08003 Barcelona
Spain
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.