{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:57:46Z","timestamp":1791201466935,"version":"4.2.0"},"reference-count":172,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Ovarian cancer remains the most lethal gynecologic malignancy, a status largely attributable to late-stage diagnosis and inevitable chemoresistance. The cGAS-STING pathway, a cornerstone of innate immune surveillance, has emerged as a critical nexus linking genomic instability to antitumor immunity\u2014a connection of particular relevance in ovarian cancer, where chromosomal instability is a defining hallmark. This review synthesizes current understanding of the cGAS-STING pathway in ovarian cancer, spanning molecular mechanisms to translational opportunities. We delineate the dualistic nature of STING signaling, which orchestrate robust T cell-mediated antitumor immunity under certain conditions yet paradoxically foster immunosuppression and tumor progression in others. Particular emphasis is placed on the intricate interplay between DNA damage repair deficiencies\u2014especially in\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    and homologous recombination\u2014and STING-dependent immune activation, which forms the mechanistic basis for the immunomodulatory effects of PARP inhibitors. We critically examine the TME, where CAFs and myeloid cells integrate STING signals to either potentiate or constrain antitumor immunity. The landscape of STING-modulating therapeutic strategies is surveyed, encompassing direct agonists, nanoparticle-based delivery platforms, and rational combinations with immune checkpoint blockade and DNA-damaging agents. Finally, we identify key unresolved questions, including the need for predictive biomarkers, strategies to overcome resistance, and the challenge of balancing therapeutic efficacy against potential toxicities. By integrating recent discoveries with established paradigms and explicitly addressing the \u201cdouble-edged sword\u201d duality of STING signaling, the stromal response, and a proposed roadmap for biomarker-guided therapeutic development, this review aims to provide a framework that distinguishes itself from prior comprehensive reviews by integrating recent discoveries with established paradigms and explicitly addressing the \u2018double-edged sword\u2019 duality of STING signaling, the stromal response, and a proposed roadmap for biomarker-guided therapeutic development.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1977503","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:19:15Z","timestamp":1791199155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The cGAS-STING pathway in ovarian cancer: from genomic instability to immunotherapeutic vulnerability"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui-Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Xian","family":"Ni","sequence":"additional","affiliation":[{"name":"Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hui","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine","place":["Zhuhai, Guangdong, China"]},{"name":"Zhuhai Hospital Affiliated to Faculty of Chinese Medicine, Macau University of Science and Technology","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine","place":["Zhuhai, Guangdong, China"]},{"name":"Zhuhai Hospital Affiliated to Faculty of Chinese Medicine, Macau University of Science and Technology","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)02463-8","article-title":"The Lancet Commission on ovarian cancer: towards equity-driven reform","volume":"407","author":"Ray-Coquard","year":"2026","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-026-00916-0","article-title":"Rethinking ovarian cancer III: the past decade and future 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