Review Article

cGAS and cancer therapy: a double-edged sword

Jia-min Du1, Mei-jia Qian1, Tao Yuan1, Rui-han Chen2, Qiao-jun He1,3, Bo Yang1, Qi Ling2, Hong Zhu1,3
1 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2 Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
3 The Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China
Correspondence to: Qi Ling:, Hong Zhu:,
DOI: 10.1038/s41401-021-00839-6
Received: 29 September 2021
Accepted: 5 December 2021
Advance online: 18 January 2022


Cyclic guanosine monophosphate-adenosine monophosphate adenosine synthetase (cGAS) is a DNA sensor that detects and binds to cytosolic DNA to generate cyclic GMP-AMP (cGAMP). As a second messenger, cGAMP mainly activates the adapter protein STING, which induces the production of type I interferons (IFNs) and inflammatory cytokines. Mounting evidence shows that cGAS is extensively involved in the innate immune response, senescence, and tumor immunity, thereby exhibiting a tumor-suppressive function, most of which is mediated by the STING pathway. In contrast, cGAS can also act as an oncogenic factor, mostly by increasing genomic instability through inhibitory effects on DNA repair, suggesting its utility as an antitumor target. This article reviews the roles and the underlying mechanisms of cGAS in cancer, particularly focusing on its dual roles in carcinogenesis and tumor progression, which are probably attributable to its classical and nonclassical functions, as well as approaches targeting cGAS for cancer therapy.
Keywords: cGAS; tumor suppression; tumor promotion; cancer therapy

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