Cancers (May 2022)

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

  • Satoru Kyo,
  • Kosuke Kanno,
  • Masahiro Takakura,
  • Hitomi Yamashita,
  • Masako Ishikawa,
  • Tomoka Ishibashi,
  • Seiya Sato,
  • Kentaro Nakayama

DOI
https://doi.org/10.3390/cancers14102504
Journal volume & issue
Vol. 14, no. 10
p. 2504

Abstract

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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.

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