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- W4300962034 abstract "Tumors with BRCA1/2 mutations or homologous recombination repair defects are sensitive to PARP inhibitors through the mechanism of synthetic lethality. Several PARP inhibitors are currently approved for ovarian, breast and pancreatic cancer in clinical practice. However, more than 40% of patients with BRCA1/2 mutations are insensitive to PARP inhibitors, which has aroused attention to the mechanism of PARP resistance and sensitization schemes. PARP inhibitor resistance is related to homologous recombination repair, stability of DNA replication forks, PARylation and epigenetic modification. Studies on epigenetics have become the hotspots of research on PARP inhibitor resistance. As an important epigenetic regulator of transcription mediated by histone methylation, EZH2 interacts with PARP through DNA homologous recombination, DNA replication, posttranslational modification, tumor immunity and other aspects. EZH2 inhibitors have been just shifting from the bench to the bedside, but the combination scheme in cancer therapy has not been fully explored yet. Recently, a revolutionary drug design combining PARP inhibitors and EZH2 inhibitors based on PROTAC techniques has shed light on the resolution of PARP inhibitor resistance. This review summarizes the interactions between EZH2 and PARP, suggests the potential PARP inhibitor sensitization effect of EZH2 inhibitors, and further discusses the potential populations that benefit from the combination of EZH2 inhibitors and PARP inhibitors." @default.
- W4300962034 created "2022-10-04" @default.
- W4300962034 creator A5017276130 @default.
- W4300962034 creator A5019257182 @default.
- W4300962034 creator A5057408531 @default.
- W4300962034 creator A5070538645 @default.
- W4300962034 date "2022-10-03" @default.
- W4300962034 modified "2023-09-26" @default.
- W4300962034 title "Combined inhibition of PARP and EZH2 for cancer treatment: Current status, opportunities, and challenges" @default.
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