激酶
DNA损伤
共济失调毛细血管扩张
癌症研究
机制(生物学)
癌症
DNA修复
合成致死
生物
医学
细胞生物学
DNA
生物化学
遗传学
认识论
哲学
作者
Liwei Wang,Songwei Jiang,Ying-Hui Yuan,Ji-Long Duan,Nian-Dong Mao,Zi Hui,Renren Bai,Tian Xie,Xiang‐Yang Ye
出处
期刊:Molecules
[MDPI AG]
日期:2022-04-12
卷期号:27 (8): 2491-2491
被引量:5
标识
DOI:10.3390/molecules27082491
摘要
As one of the key phosphatidylinositol 3-kinase-related kinases (PIKKs) family members, ataxia telangiectasia and RAD3-related protein kinase (ATR) is crucial in maintaining mammalian cell genomic integrity in DNA damage response (DDR) and repair pathways. Dysregulation of ATR has been found across different cancer types. In recent years, the inhibition of ATR has been proven to be effective in cancer therapy in preclinical and clinical studies. Importantly, tumor-specific alterations such as ATM loss and Cyclin E1 (CCNE1) amplification are more sensitive to ATR inhibition and are being exploited in synthetic lethality (SL) strategy. Besides SL, synergistic anticancer effects involving ATRi have been reported in an increasing number in recent years. This review focuses on the recent advances in different forms of synergistic antitumor effects, summarizes the pharmacological benefits and ongoing clinical trials behind the biological mechanism, and provides perspectives for future challenges and opportunities. The hope is to draw awareness to the community that targeting ATR should have great potential in developing effective anticancer medicines.
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