The activation of cGAS-STING pathway offers novel therapeutic opportunities in cancers

作者：Yumin Wang, Yonglin Zhu, Yuwei Cao, Yulin Li, Zhe Zhang, Joshua S. Fleishman, Sihang Cheng, Jichao Chen, Mingchao Ding · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1579832 · 被引用次数：20 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Cytokine Signaling Pathways and Interactions

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway are crucial elements of the type I interferon (type I IFN) response. cGAS senses both exogenous and endogenous DNA within cells, labeling cGAS-STING as a pivotal anti-tumor immunity mechanism, autoimmunity, sterile inflammatory responses, and cellular senescence. The cGAS-STING pathway, a pivotal innate immune axis, modulates tumorigenesis via diverse effector responses. Emerging evidence have shown that activating of cGAS-STING pathway functions as a therapy to kill cancers. Insights into the biology of the cGAS-STING pathway have enabled the discovery of small-molecule agents which have the potential to activate cGAS-STING axis in cancers. In this review, we first outline the principal components of the cGAS-STING signaling cascade. Then we explore recent advancements in understanding the cGAS-STING signaling pathway, with particular emphasis on its activation mechanisms and roles in tumor cancer killing. Next, we summarize a list of bioactive small-molecule compounds which activate the cGAS-STING axis, reviewing their potential applications. Finally, we discuss key limitations of this new proposed therapeutic approach and provide possible techniques to overcome them. This review highlights a novel groundbreaking therapeutic possibilities through activating cGAS-STING in cancers.