Recent Advances in Synergistic Antitumor Effects Exploited from the Inhibition of Ataxia Telangiectasia and RAD3-Related Protein Kinase (ATR).

ABSTRACT: 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 advanc

SUBMITTER: Wang LW 

PROVIDER: S-EPMC9029554 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature