Emerging Strategies for Antitumor Immunotherapy and Antiviral Defense Through the cGAS-STING Pathway

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a central regulator of innate immunity and plays a critical role in inducing pro-inflammatory cytokines and type I interferons (IFN-I). This pathway has emerged as a promising target for cancer immunotherapy and antiviral treatments. Despite its promise, the clinical translation of STING agonists is hindered by several challenges, including structural instability, high production costs, and inefficient delivery systems. These barriers underscore the urgent need for further research and innovation to optimize STING-based therapies. This review provides a comprehensive overview of the cGAS-STING pathway, focusing on its activation mechanisms and recent advances aimed at enhancing its therapeutic efficacy. Alternative activators of STING, including metal ions, exogenous DNA, and endogenous DNA, are discussed for their potential to stimulate this pathway. Furthermore, synergistic therapeutic strategies combining cGAS-STING activation with reactive oxygen species (ROS)-based treatments, such as photodynamic therapy, radiotherapy, sonodynamic therapy, and chemodynamic therapy, are highlighted. Finally, recent progress in harnessing STING activation for antiviral defense against emerging pathogens, such as SARS-CoV-2 and influenza viruses, is summarized to provide insights into the future development of cGAS-STING-targeted immunotherapies.