Project: Patient stratification based on DNA repair functionality for cancer precision medicine
| Acronym | RAD51predict (Reference Number: ERAPERMED2019-215) |
| Duration | 01/04/2020 - 31/03/2023 |
| Project Topic | Tumours with defective DNA repair by the homologous recombination repair (HRR) pathway are exquisitely sensitive to DNA damaging agents and to novel agents that block parallel pathways, as PARP inhibitors (PARPi). PARPi have been approved for the treatment of ovarian cancer (OvC) or breast cancer (BC). Current, the biomarkers being used to enrich the population of patients (pts) most likely to respond, namely the platinum-sensitive or BRCA1/2-mutated pts, have limited predictive capacity. There is a need for more specific biomarkers to guide personalized treatment. Genomic scars associated with DNA repair deficiency have been proposed as putative biomarkers. A major limitation of these assays is the lack of specificity in HRR-altered tumours once they have restored the HRR function as mechanism of drug resistance. Therefore, a functional test is needed to enrich the patient population eligible for PARPi beyond the current selection criteria. Ongoing clinical trials are evaluating the activity of PARPi in BC pts without gBRCA mutation as well as prostate (PC) and endometrial (EnC) cancers, where there is a lack of biomarkers. In the present proposal, we aim to: 1) Establish the prevalence of functional HRR deficiency and its predictive value for personalized treatment with platinum salts and PARPi in BC, OvC, PC and EnC, using the RAD51 immuno-assay and genomic assays 2) Analyse the cost-effectiveness of selecting patients for PARPi treatment based on the RAD51 assay 3) Provide functional validation of tumour/germline genomic variants of unknown significance using patient´s data, cell lines and assessment of HRR markers in the tumour 4) Integrate functional HRR data into existing public genomic databases 5) Transfer a functional research assay into a clinical-grade predictive test: development of antibodies and protocols, automatization of image analysis, and real-time monitoring in liquid biopsy (circulating tumour cells). |
| Network | ERA PerMed |
| Call | 2nd Joint Transnational Call for Proposals (2019) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca / Fundacio Privada Institut d’Investigacio Oncologica de Vall d’Hebron (VHIO) | Coordinator | Spain |
| 2 | Universitätsklinikum Gießen und Marburg GmbH | Partner | Germany |
| 3 | INSTITUT GUSTAVE ROUSSY - INSERM U981 | Partner | France |
| 4 | German Breast Group Forschungs GmbH | Partner | Germany |
| 5 | UNIVERSITÉ LAVAL | Partner | Canada |