Targeting DNA damage response pathway: recent progress of PARP inhibitors in cancer therapy
10.3969/j.issn.1001-1978.2018.02.003
- VernacularTitle:靶向DNA损伤反应途径:PARP抑制剂抗肿瘤治疗研究进展
- Author:
Yu-Jing ZHENG
1
;
Tong-Tong ZUO
;
Yu-Fei FENG
Author Information
1. 北京医院药学部
- Keywords:
DNA damage response pathway;
poly (ADP-ribose)polymerase (PARP) inhibitor;
synthetic lethality;
targeted therapy;
breast cancer susceptibility gene;
mechanism of action
- From:
Chinese Pharmacological Bulletin
2018;34(2):157-161
- CountryChina
- Language:Chinese
-
Abstract:
Genomic instability is one of the most pervasive characteristics of cancer cells,and DNA damage response (DDR) pathway plays a crucial role in genomic stability.The DDR pathway is a complex signaling network,which involves cell DNA repair,apoptosis and cell cycle regulation.Deficiencies in these repair pathways can result in several different genetic disorders,including cancer.Targeted therapy based on inhibiting the DDR pathway in cancers offers a novel therapy strategy for patients with tumors lacking specific DDR functions.Many small-mole-cule compounds targeting DDR pathway are typically developed for solid cancer therapy.The poly (ADP-ribose) polymerase (PARP) inhibitor is a kind of DDR inhibitors which exploits the principle of synthetic lethality to selectively kill cancer cells.This review highlights the molecular mechanisms of PARP inhibitor action,the progress of PARP inhibitors in cancer therapy,drug resistance and the challenge of PARP inhibitor in the future.
