Recent advances in targeting DNA repair pathways for the treatment of ovarian cancer and their clinical relevance

Int J Clin Oncol. 2017 Aug;22(4):611-618. doi: 10.1007/s10147-017-1137-7. Epub 2017 May 15.

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency.

Keywords: BRCA1; BRCA2; Hereditary breast and ovarian cancer; Homologous recombination deficiency; PARP inhibitor.

Publication types

  • Review

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics
  • Carcinoma, Ovarian Epithelial
  • Clinical Trials as Topic
  • DNA Repair / drug effects*
  • Female
  • Genetic Counseling*
  • Humans
  • Japan
  • Molecular Targeted Therapy / methods
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / genetics
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Phthalazines / pharmacology
  • Phthalazines / therapeutic use
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Poly(ADP-ribose) Polymerases / metabolism

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases
  • olaparib