The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications
Abstract Innate immunity represents the body’s first line of defense, effectively countering the invasion of external pathogens. Recent studies have highlighted the crucial role of innate immunity in antitumor defense, beyond its established function in protecting against external pathogen invasion....
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BMC
2025-04-01
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| Series: | Journal of Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s13045-025-01691-5 |
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| author | Mengzhou Shen Xianjie Jiang Qiu Peng Linda Oyang Zongyao Ren Jiewen Wang Mingjing Peng Yujuan Zhou Xiyun Deng Qianjin Liao |
| author_facet | Mengzhou Shen Xianjie Jiang Qiu Peng Linda Oyang Zongyao Ren Jiewen Wang Mingjing Peng Yujuan Zhou Xiyun Deng Qianjin Liao |
| author_sort | Mengzhou Shen |
| collection | DOAJ |
| description | Abstract Innate immunity represents the body’s first line of defense, effectively countering the invasion of external pathogens. Recent studies have highlighted the crucial role of innate immunity in antitumor defense, beyond its established function in protecting against external pathogen invasion. Enhancing innate immune signaling has emerged as a pivotal strategy in cancer therapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a key innate immune signal that activates the immune response and exerts antitumor effects; this is primarily attributed to the DNA receptor function of cGAS, which recognizes exogenous DNA to activate downstream STING signaling. This, in turn, promotes the activation of downstream targets such as IRF-3(Interferon Regulatory Factor 3) and NF-κB, leading to the secretion of type I interferons and proinflammatory cytokines, thereby increasing cellular immune activity. The activation of the cGAS-STING pathway may thus play a crucial role in enhancing anticancer immunity. In this paper, we reviewed the role of cGAS-STING signaling in anticancer immunity and its molecular mechanisms. Additionally, we briefly discuss the current applications of the cGAS-STING pathway in cancer immunity, summarize recent developments in STING agonists, and address the challenges facing the use of the cGAS-STING pathway in cancer therapy. Finally, we provide insights into the role of the cGAS‒STING pathway in cancer and propose new directions for cancer immunotherapy. |
| format | Article |
| id | doaj-art-7fbfe3dbcabf4eb38181b352a09ffebe |
| institution | OA Journals |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-7fbfe3dbcabf4eb38181b352a09ffebe2025-08-20T02:10:50ZengBMCJournal of Hematology & Oncology1756-87222025-04-0118111910.1186/s13045-025-01691-5The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implicationsMengzhou Shen0Xianjie Jiang1Qiu Peng2Linda Oyang3Zongyao Ren4Jiewen Wang5Mingjing Peng6Yujuan Zhou7Xiyun Deng8Qianjin Liao9Department of Oncology, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal University, Hunan Normal University Health Science CenterThe Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer HospitalDepartment of Oncology, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal University, Hunan Normal University Health Science CenterThe Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer HospitalSchool of Basic Medical Sciences, Hunan Normal UniversityDepartment of Oncology, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal University, Hunan Normal University Health Science CenterAbstract Innate immunity represents the body’s first line of defense, effectively countering the invasion of external pathogens. Recent studies have highlighted the crucial role of innate immunity in antitumor defense, beyond its established function in protecting against external pathogen invasion. Enhancing innate immune signaling has emerged as a pivotal strategy in cancer therapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a key innate immune signal that activates the immune response and exerts antitumor effects; this is primarily attributed to the DNA receptor function of cGAS, which recognizes exogenous DNA to activate downstream STING signaling. This, in turn, promotes the activation of downstream targets such as IRF-3(Interferon Regulatory Factor 3) and NF-κB, leading to the secretion of type I interferons and proinflammatory cytokines, thereby increasing cellular immune activity. The activation of the cGAS-STING pathway may thus play a crucial role in enhancing anticancer immunity. In this paper, we reviewed the role of cGAS-STING signaling in anticancer immunity and its molecular mechanisms. Additionally, we briefly discuss the current applications of the cGAS-STING pathway in cancer immunity, summarize recent developments in STING agonists, and address the challenges facing the use of the cGAS-STING pathway in cancer therapy. Finally, we provide insights into the role of the cGAS‒STING pathway in cancer and propose new directions for cancer immunotherapy.https://doi.org/10.1186/s13045-025-01691-5Innate immunitycGASSTINGCancer immunity |
| spellingShingle | Mengzhou Shen Xianjie Jiang Qiu Peng Linda Oyang Zongyao Ren Jiewen Wang Mingjing Peng Yujuan Zhou Xiyun Deng Qianjin Liao The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications Journal of Hematology & Oncology Innate immunity cGAS STING Cancer immunity |
| title | The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications |
| title_full | The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications |
| title_fullStr | The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications |
| title_full_unstemmed | The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications |
| title_short | The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications |
| title_sort | cgas sting pathway in cancer immunity mechanisms challenges and therapeutic implications |
| topic | Innate immunity cGAS STING Cancer immunity |
| url | https://doi.org/10.1186/s13045-025-01691-5 |
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