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

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.