Clinical Landscape of PARP Inhibitors in Ovarian Cancer: Molecular Mechanisms and Clues to Overcome Resistance

SIMPLE SUMMARY: Recent development of maintenance therapy using PARP inhibitors in ovarian cancer has led to a significant improvement in survival rates. However, resistance to these inhibitors can occur in patients, causing disease progression or relapse. Consequently, novel treatment strategies are urgently needed to overcome this resistance. This review article focuses on the precise molecular mechanisms by which PARP inhibitors exert their antitumor effects, as well as how they elicit resistance, in order to gain insight into novel therapeutic approaches to overcome PARP inhibitor resistance in ovarian cancer. ABSTRACT: The survival of patients with advanced or recurrent ovarian cancer has improved tremendously in the past decade, mainly due to the establishment of maintenance therapy with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) after conservative chemotherapies. Despite their superior efficacy, resistance to PARPis has been reported, and patients with resistance have a much worse prognosis. Therefore, the development of novel treatment strategies to overcome PARPi resistance is urgently needed. The present review article focuses on the molecular mechanisms of how PARPis exert cytotoxic effects on cancer cells through DNA repair processes, especially the genetic background and tumor microenvironment favored by PARPis. Furthermore, currently available information on PARPi resistance mechanisms is introduced and discussed to develop a novel therapeutic approach against them.