REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1579832
This article is part of the Research TopicMolecular Pathways and Signaling Molecules in Cancer Therapy: Advances and InnovationsView all 5 articles
The activation of cGAS-STING pathway offers novel therapeutic opportunities in cancers
Provisionally accepted
Yumin Wang1*
Yonglin Zhu1Yuwei Cao1Yulin Li1Zhe Zhang1Joshua S Fleishman2Sihang Cheng3Jichao Chen1Mingchao Ding1- 1Aerospace Center Hospital, Beijing, China
- 2Saint Johns University, Collegeville, Pennsylvania, United States
- 3Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China
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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 smallmolecule 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.
Keywords: CGAS, STING, agonist, Cancers Contents, Small-molecule compounds
Received: 19 Feb 2025; Accepted: 19 May 2025.
Copyright: © 2025 Wang, Zhu, Cao, Li, Zhang, Fleishman, Cheng, Chen and Ding. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yumin Wang, Aerospace Center Hospital, Beijing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.