Epigenetic regulation of cGAS and STING expression in cancer

Although cancer immunotherapy has become a successful therapeutic strategy in a certain range of solid cancer and hematological malignancies, this efficacy of immunotherapy is impeded by limited success rates due to an immunologically "cold" state. The cGAS-STING signaling pathway is an evolutionarily conserved system which can find cytoplasmic DNA to regulate the innate immune and adaptive immune response. Beyond the host defense and autoimmune disorders, recent advances have now expanded the roles of cGAS-STING that is precise activated and tight regulated to improve anticancer immunity. Mounting evidence now has shown the crucial role of epigenetic regulation in mediating the expression of key genes associated with the cGAS-STING signaling pathway. In this review, we highlight the structure and cellular localization of cGAS and STING as well as intracellular cascade reaction of cGAS-STING signal transduction. We further summarize recent findings of epigenetic regulatory mechanisms that control the expression of cGAS and STING in cancer. The review aims to offer theoretical basis and reference for targeting the epigenetic mechanisms that control cGAS and STING gene expression to promote the development of more effective combination therapeutic regimens to enhance the efficacy of cancer immunotherapy in clinical practice and cancer clinical and cancer research workers.