PARP Inhibitors in Epithelial Ovarian Cancer: State of Art and Perspectives of Clinical Research

Anticancer Res. 2016 May;36(5):2055-64.


Homologous recombination (HR) and base excision repair (BER) are two of the major DNA-repair pathways. The proteins encoded by breast-related cancer antigen (BRCA) and poly(adenosine diphosphate-ribose) polymerases (PARP) are involved in HR and BER, respectively. Tumors with HR deficiency, including those in BRCA mutation carriers, are sensitive to BER blockade via PARP inhibitors. These represent novel therapeutic tools for HR-deficient ovarian cancer, able to improve progression-free survival of women with recurrent, platinum-sensitive disease in response to recent platinum-based chemotherapy. More research is needed to assesses whether inhibitors of PARP have any role as maintenance treatment after first-line chemotherapy and as palliative treatment of platinum-resistant disease. Germline BRCA testing should be offered to all patients with ovarian cancer, regardless of age and family history. HR deficiency has been observed not only in germline BRCA mutation carriers, but also in patients with somatic mutations or epigenetic silencing of BRCA, and with loss of function of other genes. Half of all high-grade ovarian carcinomas are HR-deficient, and additional biological and clinical investigations are strongly warranted to identify patients with this subset of tumors.

Keywords: BRCA; Epithelial ovarian cancer; PARP inhibitors; base excision repair; homologous recombination; olaparib; review.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Ovarian Epithelial
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Humans
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*


  • Antineoplastic Agents
  • Poly(ADP-ribose) Polymerase Inhibitors