Opportunities and challenges of targeting cGAS-STING in cancer.

Abstract

The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway has a crucial role in detecting tumour-derived DNA, whether the pathway is generated spontaneously or induced therapeutically. Activation of the cGAS-STING pathway triggers type I interferon signalling and pro-inflammatory responses in both tumour and immune cells, establishing a delicate balance between pathological inflammation and protective immune responses. Although preclinical studies have highlighted the promise of targeting the cGAS-STING pathway to enhance antitumour immunotherapy, clinical results have fallen short of expectations. In this Review, we outline key advances in understanding the tumour-promoting and tumour-suppressive effects mediated by the cGAS-STING pathway and discuss opportunities and challenges for its integration into future cancer immunotherapy.