An Overview of PARP Resistance in Ovarian Cancer from a Molecular and Clinical Perspective

Int J Mol Sci. 2023 Jul 25;24(15):11890. doi: 10.3390/ijms241511890.

Abstract

Epithelial ovarian cancer (EOC), a primarily high-grade serous carcinoma (HGSOC), is one of the major causes of high death-to-incidence ratios of all gynecological cancers. Cytoreductive surgery and platinum-based chemotherapy represent the main treatments for this aggressive disease. Molecular characterization of HGSOC has revealed that up to 50% of cases have a deficiency in the homologous recombination repair (HRR) system, which makes these tumors sensitive to poly ADP-ribose inhibitors (PARP-is). However, drug resistance often occurs and overcoming it represents a big challenge. A number of strategies are under investigation, with the most promising being combinations of PARP-is with antiangiogenetic agents and immune checkpoint inhibitors. Moreover, new drugs targeting different pathways, including the ATR-CHK1-WEE1, the PI3K-AKT and the RAS/RAF/MEK, are under development both in phase I and II-III clinical trials. Nevertheless, there is still a long way to go, and the next few years promise to be exciting.

Keywords: PARP inhibitors; epithelial ovarian cancer; resistance.

Publication types

  • Review

MeSH terms

  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / genetics
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors

Grants and funding

This research received no external funding.