title: Leveraging DNA repair deficiency in gynecologic oncology.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Ovarian cancer has become a model for the successful translation of targeted therapy against DNA repair deficiencies in cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Walsh
authors.forename: Melissa
authors.initials: M
authors.lastname: Hodeib
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000187:drug effects*; D024682:BRCA2 Protein / Q000187:drug effects*; D045744:Cell Line, Tumor; D049914:DNA Repair-Deficiency Disorders / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors