PARP-inhibitors in epithelial ovarian cancer: Actual positioning and future expectations

Cancer Treat Rev. 2021 Sep:99:102255. doi: 10.1016/j.ctrv.2021.102255. Epub 2021 Jul 15.

Abstract

Poly-(ADP)-ribose polymerase inhibitors (PARPi) are a class of oral anticancer drugs first developed as "synthetically lethal" in cancers harboring BRCA1/BRCA2 inactivating mutations. In high-grade serous or endometrioid ovarian cancers (HGOC), PARPi demonstrated benefit as maintenance therapy in relapsing BRCA-mutated and non-mutated tumors. Recently, they extended their indications to frontline maintenance therapy. This review summarizes the current place of PARPi (i) as maintenance or single agent in recurrent disease and (ii) frontline maintenance with different settings. We reviewed the course of biomarker identification, the challenge of overcoming resistance to PARPi and future combinations with targeted therapies, including anti-angiogenic, immune checkpoint inhibitors and DNA damage response inhibitors.

Keywords: BRCA; HRD; Niraparib; Olaparib; Ovarian cancer; PARP inhibitor; Rucaparib, Veliparib.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Maintenance Chemotherapy
  • Ovarian Neoplasms / drug therapy*
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors