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

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

Content Provider	MDPI
Author	Wang, Li-Wei Jiang, Songwei Yuan, Ying-Hui Duan, Jilong Mao, Nian-Dong Hui, Zi Bai, Renren Xie, Tian Ye, Xiang-Yang
Copyright Year	2022
Description	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.
Starting Page	2491
e-ISSN	14203049
DOI	10.3390/molecules27082491
Journal	Molecules
Issue Number	8
Volume Number	27
Language	English
Publisher	MDPI
Publisher Date	2022-04-12
Access Restriction	Open
Subject Keyword	Molecules Oncology Ataxia Telangiectasia and Rad3-related Protein Kinase (atr) Dna Damage Response (ddr) Inhibitor Synergistic Effects Cancer Therapy
Content Type	Text
Resource Type	Article

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