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Review
. 2025 Dec;99(12):4883-4905.
doi: 10.1007/s00204-025-04150-9. Epub 2025 Aug 19.

Interplay of cGAS-STING and ferroptosis: crosstalk, molecular mechanisms, and therapeutic prospects

Yumin Wang #  1 , Shuang Wu #  2 , Yitong Wang #  3 , Clara Xi Wang  4 , Weihua Zheng  5 , Xia Yun  6 , Zhiji Wang  7 , Junjing Zhang #  8 , Lida Du  9 , Hongquan Wang  10   11   12
Affiliations
Review

Interplay of cGAS-STING and ferroptosis: crosstalk, molecular mechanisms, and therapeutic prospects

Yumin Wang et al. Arch Toxicol. 2025 Dec.

Erratum in

Abstract

The cGAS-STING pathway, a crucial cytosolic DNA sensor, initiates innate immune responses by detecting microbial and aberrant self-DNA. This evolutionarily conserved axis plays pivotal roles in autoimmune disorders, sterile inflammation, and cellular senescence. While transient activation confers protective immunity, dysregulated cGAS-STING signaling drives pathogenesis in inflammatory and autoimmune diseases. Emerging evidence reveals its functional convergence with diverse cell death modalities-notably ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation. Their dynamic interplay emerges as a key pathogenic mechanism across diseases, offering novel therapeutic opportunities. This review first outlines the core molecular architecture of cGAS-STING signaling and its disease roles. We then analyze the mechanisms and pathophysiological consequences of cGAS-STING-ferroptosis crosstalk in various disorders, followed by advances in therapeutic strategies targeting this interface. Finally, we discuss translational challenges and propose innovative solutions. By highlighting the therapeutic potential of pharmacologically modulating this nexus, we identify a promising treatment for diseases with inflammatory conditions.

Keywords: Antagonist; Ferroptosis; Inhibitor; Interplay; cGAS-STING.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no competing financial or nonfinancial interests to disclose. Ethical approval and consent to participation: Not applicable. Consent for publication: Not applicable.

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