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

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, res...

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Bibliographic Details
Published in:Cancers 2022-05, Vol.14 (10), p.2504
Main Authors: Kyo, Satoru, Kanno, Kosuke, Takakura, Masahiro, Yamashita, Hitomi, Ishikawa, Masako, Ishibashi, Tomoka, Sato, Seiya, Nakayama, Kentaro
Format: Article
Language:English
Subjects:
Antitumor activity
Apoptosis
Biomarkers
Cancer therapies
Chemotherapy
Cytotoxicity
DNA methylation
DNA repair
Genes
Medical prognosis
Molecular modelling
Mutation
Ovarian cancer
Patients
Poly(ADP-ribose) polymerase
Proteins
Review
Ribose
Surgery
Tumor microenvironment
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14102504