Molecular mechanism of PARP inhibitor resistance
Yi Huang1,*, Simin Chen1,*, Nan Yao1,*, Shikai Lin1, Junyi Zhang1, Chengrui Xu1, Chenxuan Wu2, Guo Chen1 and Danyang Zhou3
1 School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China
2 School of Public Health, Nanjing Medical University, Nanjing 210029, P.R. China
3 Department of Respiratory, Nanjing First Hospital, China Pharmaceutical University, Nanjing 210012, Jiangsu, P.R. China
* Equal contribution
Correspondence to:
Guo Chen, email: [email protected]
Danyang Zhou, email: [email protected]
Keywords: PARP inhibitor; synthetic lethality; BRCA1/2; homologous recombination (HR) repair
Received: July 18, 2024 Accepted: September 10, 2024 Published: September 23, 2024
ABSTRACT
Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) are the first-approved anticancer drug designed to exploit synthetic lethality. PARPi selectively kill cancer cells with homologous recombination repair deficiency (HRD), as a result, PARPi are widely employed to treated BRCA1/2-mutant ovarian, breast, pancreatic and prostate cancers. Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.
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