REVIEW article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
This article is part of the Research TopicInterplay Between Cell Death Pathways and Immune Responses: Mechanisms and Therapeutic FrontiersView all articles
Bridging Innate Immunity and Iron-Dependent Death: The Interplay Between Cyclic GMP–AMP Synthase–Stimulator of Interferon Genes Nexus and Ferroptosis in Cancer and Inflammation
Provisionally accepted
- First Affiliated Hospital of Jilin University, Changchun, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway and ferroptosis have emerged as fundamental biological mechanisms that converge in regulating cellular homeostasis and disease pathogenesis. As a central component of innate immunity, the cGAS–STING axis detects cytosolic double-stranded DNA through cGAS-mediated synthesis of 2′3′-cyclic GMP– AMP, subsequently triggering STING-dependent activation of the TBK1–IRF3 and nuclear factor-κB signaling cascades. Ferroptosis, an iron-catalyzed form of regulated cell death, is characterized by the accumulation of phospholipid hydroperoxide due to compromised antioxidant activity and dysregulated iron metabolism. Accumulating evidence has revealed the intricate crosstalk between these pathways. This review systematically explores the structural and biochemical bases of both pathways, identifies key bridging molecules that mediate their interactions, and discusses therapeutic strategies targeting this crosstalk, particularly in cancer treatment.
Keywords: Cancer, cGAS–STING, ferroptosis, Homeostasis, Immunity
Received: 12 Dec 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Hou, Chen, Chen and Wang. 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: Xiang Wang
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.