How to measure homologous recombination deficiency in ovarian cancer

Abstract

Defective DNA repair via homologous recombination (HR) is common in ovarian high grade serous carcinomas, and homologous recombination deficiency (HRD) represents an important therapeutic target in epithelial ovarian cancers (EOCs). The development of poly(ADP ribose) polymerase (PARP) inhibitors (PARPi) has been an important advance in the treatment of HR-deficient EOCs with the potential to change daily clinical practice. However, while germline and somatic mutations in BRCA1 and BRCA2 are still the most important mechanisms of HRD, alterations in other DNA repair pathways might also contribute to defective HR. In this review, we focus on current and emerging approaches for identifying and targeting HR-deficient EOCs, and discuss the challenges associated with these approaches.

Survival outcomes in patients withBRCAmutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors

“…Ovarian cancer is a heterogeneous and complex disease harboring a high degree of genomic instability and presenting an extensive range of mutations. Around 50% of high-grade serous ovarian cancers are estimated to have a deficit in the homologous recombination repair system, with 15% of patients harboring BRCA germline pathogenic variants, 6% somatic BRCA pathogenic variants, and 20% pathogenic variants, or epigenetic silencing of other homologous recombination genes including ATM, BRIP1, CHEK2, NBN, PALB2, and RAD51B-C-D/54 1–4…”