The clinical development of poly-(ADP)-ribose polymerase inhibitors (PARPi) began with the treatment of ovarian cancer patients harboring BRCA1/2 mutations and continues to be expanded to other gynecological cancers. Furthermore, The Cancer Genome Atlas (TCGA) analysis of endometrial and cervical cancers offered rationale that PARPi may be an option for treatment based on the molecular profiles of these cancer types. This review summarizes the current indications of PARPi, such as its role in the treatment and maintenance of recurrent ovarian cancer and for first-line maintenance therapy in advanced ovarian cancer. We also outline new concepts for PARPi therapy in other gynecological cancers such as endometrial and cervical cancers based on recent clinical data. Finally, we present potential future directions to continue exploring the world of PARPi resistance and combining PARPi with other therapies.
- BRCA1 protein
- BRCA2 protein
- homologous recombination
- uterine cancer
- ovarian cancer
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Contributors ACR was invited to contribute this review article and wrote the manuscript. ACR, GZDM, and RLC were responsible for conceiving and editing the manuscript. All authors approved the final manuscript before submission.
Competing interests RLC has clinical research funding from Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, and Janssenpharmaceuticals. RLC receives consulting fees from Genmab, Tesaro, Agenus, OncoMed, Novocure, Oncoquest, Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, Janssen pharmaceuticals, aravive, and OncoSec. These disclosed companies and grant funding sources had no input into the design, conduct, or preparation of the manuscript.
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Ethics approval The authors are accountable for all aspects of the work, and in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Provenance and peer review Not commissioned; internally peer reviewed.