The cGAS-STING pathway in cancer: friend or foe

The cGAS-STING pathway is crucial for recognizing aberrant DNA in the cytoplasm and activating the innate immune response. After detecting aberrant DNA in the cytoplasm, cGAS can catalyze the synthesis of cGAMP from ATP and GTP, which acts as a second messenger to engage STING and unleash type I interferons, thereby eliciting a robust antitumor immune cascade. In recent years, the role of the cGAS-STING pathway in tumor immunity has attracted widespread attention. Paradoxically, it not only activates antitumor immune responses but also promotes tumor progression under certain circumstances. This review untangles the safeguards that prevent cGAS from recognizing nuclear self-DNA, delineates the antitumor and pro-tumor mechanisms of the cGAS-STING axis, and surveys tumor immunotherapy strategies targeting this pathway.