The Role of the cGAS‐STING Signaling Pathway in Oral Mucosal Diseases: Mechanisms and Therapeutic Implications

The oral mucosa maintains a delicate immunological equilibrium amidst constant microbial and environmental challenges. Within this unique microenvironment, the cytosolic DNA-sensing cGAS-STING signaling pathway has emerged as a central innate immune hub characterized by critical duality across a spectrum of pathologies. While transient STING activation is vital for protective anti-microbial defenses and driving anti-tumor immunity in oral squamous cell carcinoma, chronic, maladaptive signaling-often driven by self-DNA accumulation-fuels pathology in autoimmune and inflammatory conditions. Consequently, emerging therapeutic strategies targeting this pathway involve dichotomous applications, utilizing STING agonists for malignancies versus inhibitors for inflammatory disorders. Safely harnessing the significant therapeutic potential of the cGAS-STING pathway for managing recalcitrant oral diseases urgently requires precise, localized modulation strategies.