The cGAS-STING pathway in fibroblast microenvironment: from molecular mechanisms to targeted therapies

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway serves as a core signaling axis for sensing cytosolic DNA and activating innate immunity. By recognizing abnormal DNA released from pathogens or tissue damage, it triggers the expression of type I interferons (IFN-I) and inflammatory cytokines, playing a pivotal role in innate immune defense, tumor immune surveillance, and tissue homeostasis regulation. As an important signaling hub in the fibroblast microenvironment, this pathway is involved in various pathophysiological processes such as antiviral immune responses, fibrosis progression, and remodeling of the tumor microenvironment (TME). In recent years, its potential in targeted therapy has become increasingly prominent: agonists of the pathway can enhance anti‑tumor immune responses, while inhibitors hold promise for alleviating aberrant inflammatory responses in fibrotic and autoimmune diseases. This review introduces the structural composition, signaling transduction process, and biological functions of the cGAS-STING pathway, and provides an overview of current research advances on related diseases, demonstrating the great potential of targeting this pathway in disease treatment.