cGAS–STING signaling pathway as a therapeutic target in human diseases

ABSTRACT: The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been extensively documented since its discovery in 2013. The cGAS-STING signaling pathway is activated upon cytoplasmic DNA stimulation and triggers innate immunity. The cGAS-STING signaling pathway is pivotal in antiviral defense and tumor immunity and significantly influences various pathological conditions. Currently, the cGAS-STING signaling pathway has been explored as a potential target for several diseases. Here, we aim to summarize the mechanisms of cGAS-STING signaling pathway activation, signal transduction, and regulation. We review the role of cGAS-STING in pathological conditions across multiple human systems. We also summarize recent progress in the development of drugs targeting this signaling pathway and ongoing clinical trials. This review may deepen our understanding of the cGAS-STING signaling pathway and unlock its translational potential for human diseases.