cGAS‑STING pathway in digestive tract cancer: From molecular mechanisms to therapeutic applications (Review)

As a classic cytosolic DNA sensor, the cyclic GMP‑AMP synthase (cGAS)‑stimulator of interferon genes (STING) pathway contributes to the secretion of multiple inflammatory molecules and functions as a suppressor or promoter in tumor development. Currently, the effect of this pathway on digestive tract cancer types remains unclear, which may be due to its paradoxical roles in different cell types. Tumor cells in digestive cancer often employ multiple mechanisms to inhibit this pathway activation, which then restricts the infiltration of antitumor immune cells and facilitates the formation of an immunosuppressive microenvironment. However, cGAS‑STING pathway activation also influences the function of multiple immune cells. For example, while it mainly potentiates the function of dendritic cells and natural killer cells in the tumor microenvironment, it can also promote macrophage polarization into the immunosuppressive M2 subset. To improve the understanding of the cGAS‑STING pathway in digestive cancer types, the present article systematically reviews the regulatory mechanism and effects of this pathway across different malignancies of the digestive system, including oral cavity, esophageal, gastric, hepatobiliary, pancreatic and colorectal cancer. Furthermore, the present review examines potential stimulatory strategies and future directions to utilize this pathway against tumors, such as inducing DNA damage, removing cell‑intrinsic inhibitory signals and direct activation by agonists. Overall, the present review aims to provide new perspectives and ideas for leveraging the cGAS‑STING pathway to exert antitumor effects by highlighting the changes and roles of this pathway in digestive tract cancer types.