PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies

J Gynecol Oncol. 2022 May;33(3):e44. doi: 10.3802/jgo.2022.33.e44. Epub 2022 Mar 8.


The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.

Keywords: Carcinoma, Ovarian Epithelial; Drug Resistance, Neoplasm; Drug Therapy, Combination; Poly(ADP-ribose) Polymerase Inhibitors.

Publication types

  • Review

MeSH terms

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


  • Poly(ADP-ribose) Polymerase Inhibitors