title: BRCA1- and BRCA2-related mutations: therapeutic implications in ovarian cancer.
abstract: Ovarian cancer is the deadliest among gynecologic cancers. Hereditary cancer related to BRCA1/2 gene mutations account for ~10%-12% of ovarian cancers. The BRCA1/2 proteins are important in homologous recombination (HR) repair of DNA. Patients with BRCA1/2 mutations have been reported to have improved chemosensitivity to platinum agents, longer disease-free intervals, and longer survivals than nonhereditary counterparts. Recent interest in poly(ADP-ribosyl) polymerase (PARP) proteins which are key components of base excision repair, has led to the development of PARP inhibitors; tumors arising in BRCA1/2 mutation carriers and/or with HR deficiency (HRD) are particularly sensitive to the action of these drugs. As 60%-80% of all advanced ovarian cancers are high-grade serous type, exhibiting HRD in at least 50% (referred as BRCAness) future antitumor strategies may depend on identifying these defects through molecular testing. Once HRD becomes amenable to routine testing, a larger group of ovarian cancer patients than are currently considered for PARP inhibitor trials, may benefit from such targeted therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, NYU School of Medicine, New York, USA.
authors.forename: B
authors.initials: B
authors.lastname: Pothuri
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006579:Heterozygote; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D011065:Poly(ADP-ribose) Polymerases
keywords: BRCA1/BRCA2; BRCAness ovarian cancer; PARP inhibitors