Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction
Journal
Frontiers in Oncology
Journal Volume
11
Date Issued
2021
Author(s)
Abstract
Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of BRCA mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development. ? Copyright ? 2021 Chiang, Lin and Cheng.
Subjects
epithelial ovarian cancer; genomic scar; homologous recombination deficiency; mutational signatures; PARP inhibitor; RAD51 foci formation
SDGs
Other Subjects
bevacizumab; BRCA1 protein; BRCA2 protein; carboplatin; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; niraparib; olaparib; paclitaxel; Rad51 protein; rucaparib; veliparib; copy number variation; DNA damage; DNA damage response; DNA methylation; DNA repair; DNA sequence; double stranded DNA break; gene expression; gene identification; gene mutation; genetic analysis; genetic counseling; genomic instability; heterozygosity loss; homologous recombination; human; immunofluorescence; intention to treat analysis; ovary carcinoma; overall survival; phase 2 clinical trial (topic); phase 3 clinical trial (topic); progression free survival; recombination repair; Review; single nucleotide polymorphism; somatic mutation; tumor suppressor gene; whole genome sequencing
Publisher
Frontiers Media S.A.
Type
review