The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications

Innate immunity represents the body's first line of defense, effectively countering the invasion of external pathogens. Recent studies have highlighted the crucial role of innate immunity in antitumor defense, beyond its established function in protecting against external pathogen invasion. Enhancing innate immune signaling has emerged as a pivotal strategy in cancer therapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a key innate immune signal that activates the immune response and exerts antitumor effects; this is primarily attributed to the DNA receptor function of cGAS, which recognizes exogenous DNA to activate downstream STING signaling. This, in turn, promotes the activation of downstream targets such as IRF-3(Interferon Regulatory Factor 3) and NF-κB, leading to the secretion of type I interferons and proinflammatory cytokines, thereby increasing cellular immune activity. The activation of the cGAS-STING pathway may thus play a crucial role in enhancing anticancer immunity. In this paper, we reviewed the role of cGAS-STING signaling in anticancer immunity and its molecular mechanisms. Additionally, we briefly discuss the current applications of the cGAS-STING pathway in cancer immunity, summarize recent developments in STING agonists, and address the challenges facing the use of the cGAS-STING pathway in cancer therapy. Finally, we provide insights into the role of the cGAS‒STING pathway in cancer and propose new directions for cancer immunotherapy.