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Review

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

1
Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan
2
Department of Obstetrics and Gynecology, Kanazawa Medical University, Kanazawa 920-0293, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Christina M. Annunziata and Adam R. Karpf
Cancers 2022, 14(10), 2504; https://doi.org/10.3390/cancers14102504
Received: 26 April 2022 / Revised: 17 May 2022 / Accepted: 18 May 2022 / Published: 19 May 2022
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.
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. View Full-Text
Keywords: ovarian cancer; PARP inhibitor; maintenance therapy; homologous recombination deficiency; replication fork; DNA damage response; cGAS/STING; cytosolic immunity ovarian cancer; PARP inhibitor; maintenance therapy; homologous recombination deficiency; replication fork; DNA damage response; cGAS/STING; cytosolic immunity
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MDPI and ACS Style

Kyo, S.; Kanno, K.; Takakura, M.; Yamashita, H.; Ishikawa, M.; Ishibashi, T.; Sato, S.; Nakayama, K. Clinical Landscape of PARP Inhibitors in Ovarian Cancer: Molecular Mechanisms and Clues to Overcome Resistance. Cancers 2022, 14, 2504. https://doi.org/10.3390/cancers14102504

AMA Style

Kyo S, Kanno K, Takakura M, Yamashita H, Ishikawa M, Ishibashi T, Sato S, Nakayama K. Clinical Landscape of PARP Inhibitors in Ovarian Cancer: Molecular Mechanisms and Clues to Overcome Resistance. Cancers. 2022; 14(10):2504. https://doi.org/10.3390/cancers14102504

Chicago/Turabian Style

Kyo, Satoru, Kosuke Kanno, Masahiro Takakura, Hitomi Yamashita, Masako Ishikawa, Tomoka Ishibashi, Seiya Sato, and Kentaro Nakayama. 2022. "Clinical Landscape of PARP Inhibitors in Ovarian Cancer: Molecular Mechanisms and Clues to Overcome Resistance" Cancers 14, no. 10: 2504. https://doi.org/10.3390/cancers14102504

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