Chinese Medical Journal article review: cGAS‑STING pathway emerges as cornerstone for next‑generation immunotherapies

The cGAS‑STING pathway detects cellular DNA to trigger type I interferons and cytokines. This review integrates mechanistic immunology with clinical oncology perspectives, dissecting pathway components, regulatory factors, and therapeutic potential for cancer and diverse diseases, bridging fundamental discoveries to clinical applications.

The innate immune system is an important component of the human immune defense and serves as the first line of defense to recognize "non-self" entities and rapidly trigger defense mechanisms. In recent years, the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway has garnered extensive attention as a key cytoplasmic DNA-sensing signaling cascade. By mediating the clearance of foreign pathogens, senescent cells, and malignant tumor cells, this pathway contributes to the maintenance of intracellular and extracellular homeostasis. Accumulating evidence has demonstrated that the cGAS-STING pathway is extensively implicated in a broad spectrum of physiological processes and pathological cascades. Consequently, in-depth investigations into the regulatory mechanisms of this pathway may yield novel insights for the clinical management of infectious diseases, inflammatory disorders, autoimmune conditions, and malignant tumors.

Dr. Xiangxiang Liu and colleagues compiled a comprehensive review of the cGAS-STING pathway's components and regulatory mechanisms, under both physiological and pathological conditions, in addition to its therapeutic applications. Their findings were made available online on November 10, 2025 of the Chinese Medical Journal .

“Emerging insights reveal the dual regulatory role of the cGAS–STING pathway in tumorigenesis, positioning this innate immune regulatory hub as a critical molecular target for cancer therapeutics,” explains Prof. Jun Lu from the School of Life Sciences at Northeast Normal University. In cancer contexts, it operates through two complementary modes: cell-autonomous mechanisms promoting tumor cell senescence or apoptosis via direct activation of death pathways, and cell-cycle arrest, and non-autonomous effects recruiting and activating dendritic cells, T cells, and NK cells to mount systemic anti-tumor immunity. This bifunctional operation makes it a uniquely complex therapeutic target that requires precise temporal and spatial modulation rather than simple on/off activation. “Thus, clinical implementation requires precision assessment systems integrating tumor molecular subtypes and pathway activation thresholds to determine optimal treatment timing,” notes Chengshi Ding, from the School of Life Sciences at Zaozhuang University.

Preclinical evidence indicates that STING agonists markedly potentiate the efficacy of radiotherapy, chemotherapy, targeted therapy, and immune checkpoint inhibitors, establishing a solid rationale for cGAS-STING-targeted anticancer strategies. “Consequently, precision reactivation strategies targeting this pathway may be a transformative improvement to approach to potentiate current immunotherapies,” concludes Dr. Na Zhang from the School of Life Sciences at Jilin University. However, clinical translation is impeded by critical bottlenecks, including heterogeneous treatment responses stemming from tumor diversity, suboptimal drug delivery efficiency, and the immunosuppressive nature of solid tumors. Overcoming these hurdles is paramount to fully exploit the therapeutic potential of cGAS-STING modulation.

Taken together, decoding the spatiotemporal dynamics of cGAS-STING signaling is essential for future progress. Understanding its real-time behavior in distinct tumor microenvironments through advanced imaging and spatial transcriptomics will enable smart interventions that maximize anti-tumor efficacy while preventing pro-tumorigenic side effects. Such technological integration could revolutionize tumor immunology and provide robust foundations for truly personalized oncology, where treatments are matched to each patient's unique tumor immune landscape. The ultimate goal is to transform cGAS-STING modulation from a blunt instrument into a precision scalpel for cancer therapy.

About the Authors

Jun Lu, Professor and PhD SupervisorDoctoral Supervisor at the School of Life Sciences, Northeast Normal University. Member of the Chinese Society for Cell Biology, member of the Cell Structure and Cell Behavior Branch of the Chinese Society for Cell Biology, and Vice Chairman of the Jilin Provincial Society for Cell Biology. Mainly engaged in the study of epigenetic mechanisms of cellular malignant transformation and cellular aging. Undertaking 21 projects including the National Key Basic Research Development Program (973 Program), National Natural Science Foundation of China, and Key Projects of Jilin Province. Published over 100 papers in journals such as Nature Aging, EMBO Journal, and Cancer Research, among which the article published in Nature Aging (2023) was selected as a Research Highlight by Nature for promotion. Received one first prize each from the "Ministry of Education Natural Science Award" and the "Jilin Province Natural Science Award", and was granted three national invention patents. Publish two books and textbooks.

Na Zhang, Associate Professor at the School of Life Sciences, Jilin University (Young Scholar Tang Aoqing), doctoral supervisor, and high-level talent in Jilin Province. Member of the Chinese Society of Cell Biology, Chinese Society of Aging, and Jilin Province Stem Cell Biology Society. Mainly engaged in research on the epigenetic mechanisms of aging and aging interventions. The research results have been published in 14 academic papers in well-known journals such as Nature Aging, EMBO Journal, and Cancer Letters. The articles published in the Nature Aging journal were selected for the "Research Highlights" column, while Huijing Xu and others from the University of Maryland in the United States published commentary articles in the "News&Views" column of the Nature Aging journal during the same period. Hosted one National Youth Science Foundation project (Class C), one Jilin Province Science and Technology Development project (General Project), and one Jilin University Excellent Youth Cultivation Program project. As a core member, participated in seven projects including the National Natural Science Foundation and provincial and ministerial level projects, and applied for five national patents.

Chengshi Ding, Professor and Master's Supervisor at the School of Life Sciences, Zaozhuang University. Director of Shandong Society of Biochemistry and Molecular Biology. Mainly engaged in research on resistance and tumor molecular engineering. Undertook more than 10 projects including the National Natural Science Foundation of China, Shandong Provincial Key R&D Program, and Shandong Provincial Natural Science Foundation, and published over 20 SCI papers. The first author won the "Huaihai Science and Technology Award" and the second prize in the first "Youth Innovation Talent Cup" scientific research and innovation selection of the Shandong Society of Biochemistry and Molecular Biology, and was granted 3 national invention patents. Edited and published one textbook.

Xiangxiang Liu, lecturer at the School of Life Sciences, Zaozhuang University. Mainly engaged in research on protein post-translational modifications in tumor cell proliferation and metastasis related diseases; Screening of epigenetic enzyme inhibitors and study of their anti-tumor activity. Participated in 1 National Natural Science Foundation of China , 1 Shandong Natural Science Foundation Youth Projectand and 1 doctoral research fund of Zaozhuang University. Published 6 academic papers in well-known journals such as Cancer Letters and Cell Death&Disease.