Christine S Walsh1, Melissa Hodeib. 1. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Abstract
PURPOSE OF REVIEW: The review discusses DNA repair deficiencies in ovarian cancer and how this has become the target for poly (ADP-ribose) polymerase (PARP) inhibition as a successful therapeutic strategy. RECENT FINDINGS: Hereditary ovarian cancers arise from germline mutations in BRCA1, BRCA2, or other important genes in the DNA repair process of homologous recombination. Sporadic ovarian cancers can also acquire a phenotype of homologous recombination deficiency through various other mechanisms. Recent studies have found the class of drugs called PARP inhibitors to selectively target ovarian cancers with homologous recombination deficiency. There are eight PARP inhibitors in various phases of clinical development with four being actively studied in phase III trials in ovarian cancer. In December 2014, the first-in-human PARP inhibitor olaparib was approved for ovarian cancer patients with two different clinical indications in Europe and the United States. SUMMARY: Ovarian cancer has become a model for the successful translation of targeted therapy against DNA repair deficiencies in cancer.
PURPOSE OF REVIEW: The review discusses DNA repair deficiencies in ovarian cancer and how this has become the target for poly (ADP-ribose) polymerase (PARP) inhibition as a successful therapeutic strategy. RECENT FINDINGS:Hereditary ovarian cancers arise from germline mutations in BRCA1, BRCA2, or other important genes in the DNA repair process of homologous recombination. Sporadic ovarian cancers can also acquire a phenotype of homologous recombination deficiency through various other mechanisms. Recent studies have found the class of drugs called PARP inhibitors to selectively target ovarian cancers with homologous recombination deficiency. There are eight PARP inhibitors in various phases of clinical development with four being actively studied in phase III trials in ovarian cancer. In December 2014, the first-in-humanPARP inhibitor olaparib was approved for ovarian cancerpatients with two different clinical indications in Europe and the United States. SUMMARY:Ovarian cancer has become a model for the successful translation of targeted therapy against DNA repair deficiencies in cancer.