Homologous recombination deficiency in epithelial ovarian cancer

SummarySince the introduction of poly-ADP-ribose polymerase (PARP) inhibitor therapy for epithelial ovarian cancer (EOC) patients, testing for aberrations of homologous recombination (HR) repair as a predictive biomarker of therapy response has become an area of particular clinical interest. As HR represents a  crucial repair pathway of otherwise possibly lethal DNA double strand breaks, its deficiency triggers a phenotypic behavior of tumor cells resulting in the accumulation of genetic damage. PARP inhibitors target this emerging genomic instability by fostering DNA strand breaks. Whereas testing for mutations of the tumor-suppressor genesBRCA  1 andBRCA  2 as a pivotal part of the HR apparatus has entered clinical routine, approximately 30% more high-grade EOC patients harbor aberrations of the HR pathway other thanBRCAmutations and may therefore respond to PARP inhibition therapy. In recent years, several double-blind, placebo-controlled trials investigating sizeable patient cohorts have reported positive results of PARP inhibitor therapy response in HR-positive patient subgroups. Therefore, introducing HR testing in both the primary and recurrent setting as a biomarker for PARP inhibitor response may expand the range of patients who may profit from this therapeutic option beyond BRCA-mutated tumors.
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research