Breaking barriers: The cGAS‐STING pathway as a novel frontier in cancer immunotherapy

Oct 13, 2025Cancer communications (London, England)

The cGAS-STING pathway as a new target for cancer immunotherapy

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Abstract

The - signaling pathway is associated with regulating diverse cellular processes such as cellular senescence, autophagy, and tumor immunosurveillance.

Dysregulation of the cGAS-STING pathway may correlate with the development and progression of various diseases, including autoimmune disorders and cancer.
The cGAS-STING pathway has dual roles in cancer immunity, potentially triggering both antitumor and immunosuppressive effects.
Recent advances in therapeutic strategies targeting the cGAS-STING pathway include nanomaterials, antibody-drug conjugates, and engineered bacteria.
Challenges remain in the development of effective therapies targeting the cGAS-STING pathway.

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Since its discovery, the cyclic GMP-AMP synthase ()-stimulator of the interferon gene () signaling pathway has been considered a pivotal component of innate immunity and a promising target for cancer immunotherapy. Beyond its canonical role in pathogen defense, accumulating evidence has demonstrated that the cGAS-STING pathway critically regulates diverse cellular processes, including cellular senescence, autophagy, cell death, and tumor immunosurveillance; therefore, dysregulation of this pathway correlates with the pathogenesis and progression of various human diseases, ranging from autoimmune and inflammatory disorders to cancer. Herein, we reviewed the regulatory mechanisms and cellular functions of the cGAS-STING pathway, highlighting its essential role in maintaining immune homeostasis. We systematically discussed the dual roles of the cGAS-STING pathway in cancer immunity, in which it triggers both antitumor and immunosuppressive effects. Finally, we summarized the recent advances and challenges in therapeutic strategies targeting the cGAS-STING pathway and discussed the next generation of therapies, including nanomaterials, antibody-drug conjugates, engineered bacteria, alternative strategies, optogenetic approaches, and combination strategies. We hope that our efforts will advance the understanding of the fundamental principles of innate immune recognition and response, and provide novel directions for improving the clinical outcomes of cGAS-STING-targeted therapies.

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Breaking barriers: The cGAS‐STING pathway as a novel frontier in cancer immunotherapy

Abstract

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