cGAS/STING Pathway in Cancer: Jekyll and Hyde Story of Cancer Immune Response

Abstract

The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon genes(STING) pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis. This review highlights our current understanding of cGAS/STING pathway in cancer, its therapeutic targeting and potential alternate approaches to target this pathway. Optimal therapeutic targeting and artificial tunability of this pathway still demand in depth understanding of cGAS/STING pathway regulation and homeostasis.

Keywords: Cyclic guanosine monophosphate–adenosine monophosphate (cGAMP); STING; cGAS; cancer; cancer immunotherapy; immunity.

Figure 1

Schematic representation of Cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon genes(STING) signaling mediated T cell priming in tumor microenvironment. A and G denotes Adenosine monophosphate (AMP) and Guanosine monophosphate (GMP) respectively.