cGAS-STING pathway in lung cancer and emerging therapeutic approaches.

Lung cancer is an aggressive malignancy with one of the highest mortality rates among cancers. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, a central mediator of immunity, is frequently attenuated in lung cancer through a variety of mechanisms. This attenuation facilitates immune evasion while creating both a significant clinical challenge and a major therapeutic opportunity. Here, we analyze how lung cancer subtypes disrupt the cGAS-STING pathway and evaluate emerging therapeutic strategies, including STING agonism, epigenetic reactivation, metabolic and enzymatic targeting, and combination regimens with immunotherapy and radiotherapy. Precision tuning of cGAS-STING activity offers a promising avenue to reshape the tumor microenvironment and overcome tumor progression in lung cancer.