Objective
Breast and ovarian carcinomas are aggressive tumors with few treatment options and high recurrence rates. About half of these tumors shows defects in homologous recombination (HR) repair. Defect in HR (HRD) causes genomic instability and dependence on poly (ADP-ribose) polymerase (PARP)-mediated DNA repair. As a result, PARP inhibitors (PARPi) are now widely used for the treatment of these tumors. However, resistance to PARPi is emerging as the major obstacle to clinical effectiveness. Consequently, many patients run out of treatment options and succumb to the disease. This prompts the development of novel therapeutics.
Beyond its well-known functions in regulating metabolic processes, we discovered that enzyme X maintains genomic stability in HRD cells. Enzyme X inhibition kills HRD cells without affecting HR-proficient cell survival pointing to a synthetic lethal interaction between enzyme X and HR genes. Moreover, we showed that enzyme X functions independently of PARP in the survival of HRD cells. As a result, enzyme X inhibition kills naive and PARPi-resistant HRD cells. Thus, targeting this enzyme has the potential to provide a new cure for HRD tumors.
No inhibitors nor patents on enzyme X exist. HRD tumors being a major economic burden worldwide, developing enzyme X inhibitors has high innovation and financial reward potentials. By screening chemical libraries, we identified a top hit inhibitor of enzyme X. Our TargetBRCA project aims at improving potency and specificity of our molecule inhibitor and provides a proof-of-concept on its use as a cure for HRD tumors. TargetBRCA relies on complementary teams of crystallographers, chemists and specialists of HRD tumor biology and associates structure-aided drug design with the use of preclinical in vivo models. Our ultimate goal is to foster the development of a clinical-grade inhibitor to be used for the treatment of HRD tumors either by licensing and co-development partnerships, or by the creation of a start-up.
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
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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-ERC-POC - HORIZON ERC Proof of Concept Grants
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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) ERC-2022-POC1
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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.
75231 Paris
France
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.