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Fighting Resistance: Post-PARP Inhibitor Treatment Strategies in Ovarian Cancer

Overview
Specialty Oncology
Date 2023 Mar 6
PMID 36872947
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Abstract

Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a therapeutic milestone in the management of epithelial ovarian cancer. The concept of 'synthetic lethality' is exploited by PARPi in tumors with defects in DNA repair pathways, particularly homologous recombination deficiency. The use of PARPis has been increasing since its approval as maintenance therapy, particularly in the first-line setting. Therefore, resistance to PARPi is an emerging issue in clinical practice. It brings an urgent need to elucidate and identify the mechanisms of PARPi resistance. Ongoing studies address this challenge and investigate potential therapeutic strategies to prevent, overcome, or re-sensitize tumor cells to PARPi. This review aims to summarize the mechanisms of resistance to PARPi, discuss emerging strategies to treat patients post-PARPi progression, and discuss potential biomarkers of resistance.

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References
1.
Parsels L, Karnak D, Parsels J, Zhang Q, Velez-Padilla J, Reichert Z . PARP1 Trapping and DNA Replication Stress Enhance Radiosensitization with Combined WEE1 and PARP Inhibitors. Mol Cancer Res. 2017; 16(2):222-232. PMC: 5805596. DOI: 10.1158/1541-7786.MCR-17-0455. View

2.
Flynn M, Ledermann J . Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer. Cancer Drug Resist. 2022; 5(2):424-435. PMC: 9255242. DOI: 10.20517/cdr.2022.13. View

3.
Rondinelli B, Gogola E, Yucel H, Duarte A, van de Ven M, van der Sluijs R . EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nat Cell Biol. 2017; 19(11):1371-1378. DOI: 10.1038/ncb3626. View

4.
Clements K, Schleicher E, Thakar T, Hale A, Dhoonmoon A, Tolman N . Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens. Nat Commun. 2020; 11(1):6118. PMC: 7704667. DOI: 10.1038/s41467-020-19961-w. View

5.
Xu G, Chapman J, Brandsma I, Yuan J, Mistrik M, Bouwman P . REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature. 2015; 521(7553):541-544. PMC: 4671316. DOI: 10.1038/nature14328. View