Clinical Qualification of DNA Repair Defects as Biomarkers in Metastatic Prostate Cancer Using Integrated Genomics and Tissue Based Functional Assays

ABSTRACT

We and others previously described an enrichment for somatic and germline alterations in DNA damage repair (DDR) genes among men with metastatic prostate cancer. Several recent clinical studies have indicated many of these patients could benefit from precision medicine strategies with PARP inhibitors and DNA damaging agents. In this project, our teams would investigate genomic, transcriptomic and protein related functional signatures for a more accurate sub-classification of prostate cancers associated to DDR defects, aiming for a more precise patient care. The project is divided in 3 main aims: 1) testing the prognostic value of somatic DDR defects in a retrospective cohort of tumor biopsies, 2) developing multi-omics signatures based on prospective analyses of metastatic biopsies and 3) clinical validation of these biomarkers in a clinical trial using carboplatin as DNA damaging chemotherapy.