{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:31Z","timestamp":1789103251873,"version":"build-2803163510"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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. Mol. Biosci."],"abstract":"<jats:p>Immune checkpoint blockade produces durable benefit mainly in microsatellite instability-high\/mismatch repair-deficient (MSI-H\/dMMR) colorectal cancer (CRC), whereas most microsatellite-stable\/mismatch repair-proficient (MSS\/pMMR) tumors remain poorly inflamed and resistant to immunotherapy. This focused narrative review examines how mitochondrial DNA (mtDNA)-derived danger signals engage the cGAS-STING pathway in CRC, distinguishes canonical DNA sensing from noncanonical STING activation and STING-independent cGAS functions, and evaluates therapeutic strategies that modulate this axis. We qualitatively synthesize peer-reviewed mechanistic and translational studies addressing mtDNA release, pathway routing, cellular context, therapeutic targeting, and biomarkers in CRC, while drawing on pan-cancer and DNA-damage studies only when they clarify pathway architecture or translational constraints. No new experimental, patient-level, or case-series data are presented. Current evidence indicates that biological outcome depends on more than pathway activation alone. Signal amplitude and duration, STING trafficking and proteostasis, downstream IRF3- versus NF-\u03baB-biased signaling, autophagy and mitophagy, metabolic state, pathway abundance, and responding cell type collectively determine whether activation supports antitumor immunity or chronic inflammation and immune suppression. Nuclear DNA damage can also activate noncanonical STING programs independently of cGAS, whereas cGAS can exert STING-independent functions. Upstream mtDNA-origin interventions may provide a more localized route to pathway activation by exploiting tumor mitochondrial stress, but cGAS is not intrinsically mtDNA-specific and any safety advantage over direct STING agonism remains unproven clinically. Clinical translation should therefore prioritize origin-resolved biomarkers, cell-specific pharmacodynamic readouts, tumor-localized and transient pathway modulation, and biomarker-stratified trials.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1939425","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:31:17Z","timestamp":1789101077000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The mitochondrial DNA-cGAS-STING axis in colorectal cancer: a focused review of context-dependent roles and therapeutic opportunities"],"prefix":"10.3389","volume":"13","author":[{"given":"Huayang","family":"Gui","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"eaat8657","DOI":"10.1126\/science.aat8657","article-title":"cGAS in action: expanding roles in immunity and inflammation","volume":"363","author":"Ablasser","year":"2019","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"110315","DOI":"10.1016\/j.ygeno.2022.110315","article-title":"Single-cell mtDNA heteroplasmy in colorectal cancer","volume":"114","author":"Almeida","year":"2022","journal-title":"Genomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"156158","DOI":"10.1016\/j.prp.2025.156158","article-title":"Mitochondrial DNA release and cGAS-STING activation: emerging insights into anti-tumor immunity","volume":"273","author":"Aloraini","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"B4","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/290457a0","article-title":"Sequence and organization of the human mitochondrial genome","volume":"290","author":"Anderson","year":"1981","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andr\u00e9","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1795882","DOI":"10.3389\/fmicb.2026.1795882","article-title":"Microbial dysbiosis drives colorectal carcinogenesis via integrated inflammatory, metabolic, and biofilm pathways","volume":"17","author":"Bachir","year":"2026","journal-title":"Front. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"Ca. Cancer J. Clin."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6320","DOI":"10.1245\/s10434-024-15759-y","article-title":"Mitochondrial DNA copy number as a biomarker for guiding adjuvant chemotherapy in stages II and III colorectal cancer patients with mismatch repair deficiency: seeking benefits and avoiding harms","volume":"31","author":"Chen","year":"","journal-title":"Ann. Surg. Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/s41416-023-02568-5","article-title":"Mitochondrial DNA copy number plays opposing roles in T-lymphocyte infiltration of colorectal cancer based on mismatch repair status: new directions for immunotherapy?","volume":"130","author":"Chen","year":"","journal-title":"Br. J. Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1709908","DOI":"10.3389\/fimmu.2025.1709908","article-title":"cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer","volume":"16","author":"Chen","year":"2025","journal-title":"Front. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"86","DOI":"10.20892\/j.issn.2095-3941.2025.0282","article-title":"Migration and invasion inhibitory protein inhibits M2 macrophage polarization to suppress colorectal cancer progression through the STING-NF\u03baB2-IL10 axis","volume":"23","author":"Chen","year":"2026","journal-title":"Cancer Biol. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3286","DOI":"10.1111\/cas.70196","article-title":"Activation of cGAS-STING pathway by DAI-triggered ferroptosis in CRC cells reprograms TAMs balance to promote anti-tumor immunity","volume":"116","author":"Cheng","year":"2025","journal-title":"Cancer Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e2524594123","DOI":"10.1073\/pnas.2524594123","article-title":"Immune cell-intrinsic STING activation drives tumor ferroptosis via AA-mediated suppression of ACSL4 lactylation in colorectal cancer","volume":"123","author":"Ding","year":"2026","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.1038\/s41388-026-03839-0","article-title":"LncRNA 606938-TFAM axis drives oxidative stress and activates cGAS-STING pathway-mediated antitumor immunity to restrain colorectal cancer progression","volume":"45","author":"Du","year":"2026","journal-title":"Oncogene"},{"key":"B16","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.molcel.2018.07.034","article-title":"Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-\u03baB signaling after nuclear DNA damage","volume":"71","author":"Dunphy","year":"2018","journal-title":"Mol. Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/s41575-019-0126-x","article-title":"Immunotherapy in colorectal cancer: rationale, challenges and potential","volume":"16","author":"Ganesh","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6800","DOI":"10.1021\/acs.nanolett.5c05538","article-title":"Activatable polymeric STING agonist-gold nanorod conjugate driving STING signaling and immunogenic activation in colorectal cancer immunotherapy","volume":"26","author":"Gao","year":"2026","journal-title":"Nano Lett."},{"key":"B19","doi-asserted-by":"publisher","first-page":"324","DOI":"10.7150\/thno.78718","article-title":"Mutational signature of mtDNA confers mechanistic insight into oxidative metabolism remodeling in colorectal cancer","volume":"13","author":"Guo","year":"2023","journal-title":"Theranostics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"115032","DOI":"10.1016\/j.jconrel.2026.115032","article-title":"STING agonist-primed supramolecular oncolytic hydrogel vaccine for tuning tumors against themselves","volume":"395","author":"Guo","year":"2026","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-026-03036-2","article-title":"Specific bile acids can elicit the type-I interferon response through the cGAS-STING pathway","author":"He","year":"2026","journal-title":"Cell Commun. Signal. CCS."},{"key":"B22","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41580-020-0244-x","article-title":"Molecular mechanisms and cellular functions of cGAS-STING signalling","volume":"21","author":"Hopfner","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e23182","DOI":"10.1002\/advs.202523182","article-title":"TME\/NIR dual-responsive zinc-based targeted nanoagonist for multimodal amplification of STING-mediated cancer immunotherapy","author":"Hu","year":"2026","journal-title":"Adv. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3390\/antiox13060679","article-title":"Lovastatin-induced mitochondrial oxidative stress leads to the release of mtDNA to promote apoptosis by activating cGAS-STING pathway in human colorectal cancer cells","volume":"13","author":"Huang","year":"2024","journal-title":"Antioxidants"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e22826","DOI":"10.1002\/advs.202522826","article-title":"EEPD1 inhibition unleashes antitumor immunity in colorectal cancer by activating the cGAS-STING pathway","volume":"13","author":"Huo","year":"2026","journal-title":"Adv. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"124183","DOI":"10.1016\/j.biomaterials.2026.124183","article-title":"A hybrid nanoadjuvant cascading activation of the cGAS-STING-IFN-I pathway to enhance radio-immunotherapy","volume":"333","author":"Jiang","year":"2026","journal-title":"Biomaterials"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1007\/s00262-022-03200-w","article-title":"Role of the cGAS-STING pathway in regulating the tumor-immune microenvironment in dMMR\/MSI colorectal cancer","volume":"71","author":"Kaneta","year":"2022","journal-title":"Cancer Immunol. Immunother. CII"},{"key":"B28","doi-asserted-by":"publisher","first-page":"19234","DOI":"10.1038\/s41598-025-03924-6","article-title":"Downregulation of cGAS\/STING expression in tumor cells by cancer-associated fibroblasts in colorectal cancer","volume":"15","author":"Kanoda","year":"2025","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"153093","DOI":"10.1016\/j.bbrc.2025.153093","article-title":"Dual PI3K\u03b4\/\u03b3 inhibition enhances radiotherapy-induced antitumor immunity via macrophage-dependent cGAS-STING-type I interferon signaling","volume":"795","author":"Kim","year":"2026","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"112753","DOI":"10.4251\/wjgo.v17.i12.112753","article-title":"Interlaced roles of mitochondrial DNA in colorectal cancer: liquid-biopsy biomarkers, nuclear mtDNA-driven genomic instability, and mito-encoded micro peptide signaling","volume":"17","author":"Koo","year":"2025","journal-title":"World J. Gastrointest. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1158\/2159-8290.CD-19-0761","article-title":"The cytosolic DNA-sensing cGAS-STING pathway in cancer","volume":"10","author":"Kwon","year":"2020","journal-title":"Cancer Discov."},{"key":"B32","doi-asserted-by":"publisher","first-page":"108219","DOI":"10.1016\/j.phrs.2026.108219","article-title":"Microbiota-targeted nanoplatforms for colorectal cancer immunotherapy","volume":"228","author":"Li","year":"","journal-title":"Pharmacol. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.3390\/cancers18111786","article-title":"Mitochondrial metabolic reprogramming in colorectal cancer-associated fibroblasts: an up-to-date review","volume":"18","author":"Li","year":"","journal-title":"Cancers"},{"key":"B34","doi-asserted-by":"publisher","first-page":"50237","DOI":"10.1021\/acsami.5c09122","article-title":"Orally deliverable engineered porphyrin nanohybrids activate the cGAS-STING axis and enable fusobacterium-specific targeting for robust immune remodeling and colorectal cancer regression","volume":"17","author":"Liang","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e199716","DOI":"10.1172\/JCI199716","article-title":"Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity","volume":"136","author":"Liao","year":"2026","journal-title":"J. Clin. Invest."},{"key":"B36","doi-asserted-by":"publisher","first-page":"10360","DOI":"10.1021\/acs.jmedchem.5c03402","article-title":"Overcoming STING-driven immunosuppression with a bifunctional STING Agonist\/PD-L1 inhibitor for enhanced antitumor immunity","volume":"69","author":"Lin","year":"","journal-title":"J. Med. Chem."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-026-03214-8","article-title":"The emerging nexus of STING signaling and ferroptosis: from mechanisms to therapeutic opportunities","author":"Lin","year":"","journal-title":"Cell Death Discov."},{"key":"B38","doi-asserted-by":"publisher","first-page":"8545428","DOI":"10.1155\/humu\/8545428","article-title":"PLSCR3 deficiency triggers mtDNA-Driven cGAS-STING activation to potentiate antitumor immunity in colorectal cancer","volume":"2026","author":"Ling","year":"2026","journal-title":"Hum. Mutat."},{"key":"B39","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1186\/s12885-023-10748-y","article-title":"Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer","volume":"23","author":"Linke","year":"2023","journal-title":"BMC Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12964-023-01466-w","article-title":"cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation","volume":"22","author":"Liu","year":"2024","journal-title":"Cell Commun. Signal. CCS"},{"key":"B41","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.actbio.2026.04.007","article-title":"Salmonella biomimetic janus nanorobots reinvigorate colorectal cancer radio-immunotherapy by glycolysis inhibition and cGAS-STING activation","volume":"215","author":"Liu","year":"2026","journal-title":"Acta Biomater."},{"key":"B42","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41568-025-00894-9","article-title":"Opportunities and challenges of targeting cGAS-STING in cancer","volume":"26","author":"Lu","year":"2026","journal-title":"Nat. Rev. Cancer"},{"key":"B43","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40364-024-00606-9","article-title":"Gasdermin E benefits CD8+T cell mediated anti-immunity through mitochondrial damage to activate cGAS-STING-interferon\u03b2 axis in colorectal cancer","volume":"12","author":"Luo","year":"2024","journal-title":"Biomark. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"117012","DOI":"10.1016\/j.celrep.2026.117012","article-title":"Cytosolic DNA structures produced by mismatch repair deficiency coordinate anti-tumor immunity in colorectal cancer","volume":"45","author":"Mosley","year":"2026","journal-title":"Cell Rep."},{"key":"B45","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41392-026-02596-6","article-title":"Unleashing the potential of bimetallic nanobomb-mediated STING pathway to enhance bispecific T-cell engager against colorectal cancer photo-immunotherapy","volume":"11","author":"Mu","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.3390\/cancers15102826","article-title":"The impact of tumor cell-intrinsic expression of cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes (STING) on the infiltration of CD8+ T cells and clinical outcomes in mismatch repair proficient\/microsatellite stable colorectal cancer","volume":"15","author":"Nakajima","year":"2023","journal-title":"Cancers"},{"key":"B47","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1200\/JCO.2017.76.9901","article-title":"Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-Deficient\/Microsatellite instability-high metastatic colorectal cancer","volume":"36","author":"Overman","year":"2018","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e2403309","DOI":"10.1002\/adhm.202403309","article-title":"Enhanced cGAS-STING activation and immune response by LPDAM platform-based lapachone-chemical-photothermal synergistic therapy for colorectal cancer","volume":"14","author":"Pan","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"B49","doi-asserted-by":"publisher","first-page":"115009","DOI":"10.1016\/j.isci.2026.115009","article-title":"C5aR1 and cGAS\/STING and their possible involvement in radiosensitivity of colorectal cancer","volume":"29","author":"Pham","year":"2026","journal-title":"iScience"},{"key":"B6","doi-asserted-by":"publisher","first-page":"103376","DOI":"10.1016\/j.mtbio.2026.103376","article-title":"Engineering manganese-based immune amplifier for chemoimmunotherapy of peritoneal metastatic colorectal cancer","volume":"39","author":"Qiu","year":"2026","journal-title":"Mater. Today Bio"},{"key":"B50","doi-asserted-by":"publisher","first-page":"101855","DOI":"10.1016\/j.gendis.2025.101855","article-title":"Context-dependent actions of STING pathway in colitis and associated colon cancer","volume":"13","author":"Qu","year":"","journal-title":"Genes. Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"17717","DOI":"10.1038\/s41598-026-48815-6","article-title":"SLC30A10 downregulation is associated with cGAS-STING pathway activation in colorectal tubular adenoma","volume":"16","author":"Qu","year":"","journal-title":"Sci. Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e49799","DOI":"10.15252\/embr.201949799","article-title":"Mitochondrial DNA in inflammation and immunity","volume":"21","author":"Riley","year":"2020","journal-title":"EMBO Rep."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1158\/0008-5472.CAN-23-1788","article-title":"Serine depletion promotes antitumor immunity by activating mitochondrial DNA-mediated cGAS-STING signaling","volume":"84","author":"Saha","year":"2024","journal-title":"Cancer Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.2174\/0109298673316839240829075650","article-title":"Mitochondrial DNA mutations in colorectal cancer stem cells: implications for tumor dynamics and therapeutic strategies","volume":"33","author":"Shakhpazyan","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"154218","DOI":"10.1016\/j.bbrc.2026.154218","article-title":"Mitochondrial genome alterations in cancer: from mutations and epigenetics to targeted therapiesack","volume":"829","author":"Shetty","year":"2026","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B56","doi-asserted-by":"publisher","first-page":"116692","DOI":"10.1016\/j.intimp.2026.116692","article-title":"STING-activating nanomedicines in cancer immunotherapy: mechanisms, design, and therapeutic outcomes","volume":"180","author":"Singhai","year":"2026","journal-title":"Int. Immunopharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"124015","DOI":"10.1016\/j.biomaterials.2026.124015","article-title":"Methionine-depleting engineered probiotics promote PD-L1 antibody immunotherapy by activating the STING pathway","volume":"330","author":"Sun","year":"2026","journal-title":"Biomaterials"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1093\/brain\/awag037","article-title":"Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis","volume":"149","author":"Szabo","year":"2026","journal-title":"Brain J. Neurol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"113212","DOI":"10.1016\/j.jinorgbio.2026.113212","article-title":"Oxaliplatin-artesunate conjugate intensifies suppression on colorectal cancer by boosting antitumor immunity","volume":"277","author":"Tan","year":"2026","journal-title":"J. Inorg. Biochem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"218132","DOI":"10.1016\/j.canlet.2025.218132","article-title":"Targeting DRP1 promotes radiotherapy-induced antitumor immunity via mitochondrial DNA-mediated cGAS-STING signaling in KRAS-mutated colorectal cancer","volume":"637","author":"Tsai","year":"2026","journal-title":"Cancer Lett."},{"key":"B61","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1186\/s12951-026-04267-8","article-title":"Multifunctional copper-based nanoparticles potentiate colorectal cancer immunotherapy via synergistic metabolic remodeling and cGAS-STING pathway activation","volume":"24","author":"Tu","year":"2026","journal-title":"J. Nanobiotechnology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1093\/mutage\/geag009","article-title":"Changes in telomere length and mitochondrial DNA copy number in the colorectal adenoma-carcinoma sequence","volume":"41","author":"Valickova","year":"2026","journal-title":"Mutagenesis"},{"key":"B63","doi-asserted-by":"publisher","first-page":"114316","DOI":"10.1016\/j.yexcr.2024.114316","article-title":"cGAS regulates metabolic reprogramming independently of STING pathway in colorectal cancer","volume":"443","author":"Wang","year":"2024","journal-title":"Exp. Cell Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.actbio.2025.08.021","article-title":"MIL-100(Fe)-based Co-delivery platform as cascade synergistic chemotherapy and immunotherapy agents for colorectal cancer via the cGAS-STING pathway","volume":"204","author":"Wang","year":"","journal-title":"Acta Biomater."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1684770","DOI":"10.3389\/fonc.2025.1684770","article-title":"Novel mtDNA methylation-associated prognostic signatures in colorectal cancer","volume":"15","author":"Wang","year":"","journal-title":"Front. Oncol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1136\/gutjnl-2024-333533","article-title":"Early detection of colorectal cancer using aberrant circulating cell-free mitochondrial DNA fragmentomics","volume":"74","author":"Wang","year":"","journal-title":"Gut"},{"key":"B67","doi-asserted-by":"publisher","first-page":"114987","DOI":"10.1016\/j.yexcr.2026.114987","article-title":"The cGAS-STING signaling pathway mediates pyroptosis in colonic epithelial cells and accelerates the progression of CAC","volume":"458","author":"Wang","year":"","journal-title":"Exp. Cell Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"e013697","DOI":"10.1136\/jitc-2025-013697","article-title":"Targeting macrophage-derived SPP1 enhances CD8 T cell infiltration via ROS-DNA fragment\/cGAS-STING\/STAT1-mediated CXCL9\/10 in tumor microenvironment","volume":"14","author":"Wang","year":"","journal-title":"J. Immunother. Cancer"},{"key":"B69","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nature14156","article-title":"Mitochondrial DNA stress primes the antiviral innate immune response","volume":"520","author":"West","year":"2015","journal-title":"Nature"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.21037\/jgo-2025-592","article-title":"Andrographolide potentiates anti-tumor immunity in colorectal cancer (CRC) by targeting voltage-dependent anion channel (VDAC) and activating the cGAS-STING axis","volume":"16","author":"Wu","year":"","journal-title":"J. Gastrointest. Oncol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"bgaf092","DOI":"10.1093\/carcin\/bgaf092","article-title":"LncRNA-encoded peptide LRRC75A-AS1-ORF3 suppresses anti-tumor immunity in colorectal cancer through mitophagy-mediated attenuation of cGAS-STING signaling","volume":"47","author":"Wu","year":"","journal-title":"Carcinogenesis"},{"key":"B72","doi-asserted-by":"publisher","first-page":"123854","DOI":"10.1016\/j.lfs.2025.123854","article-title":"Mitochondrial p32-mediated regulation of p-TBK1 affects the radiosensitivity of colorectal cancer","volume":"379","author":"Wu","year":"","journal-title":"Life Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"189249","DOI":"10.1016\/j.bbcan.2024.189249","article-title":"Mitochondrial DNA-activated cGAS-STING pathway in cancer: mechanisms and therapeutic implications","volume":"1880","author":"Xia","year":"2025","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e10610","DOI":"10.1002\/btm2.10610","article-title":"Curcumin\/L-OHP co-loaded HAP for cGAS-STING pathway activation to enhance the natural immune response in colorectal cancer","volume":"9","author":"Xiao","year":"2024","journal-title":"Bioeng. Transl. Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e2531588123","DOI":"10.1073\/pnas.2531588123","article-title":"A BCG hydrogel enables localized NOD2\/STING activation to overcome resistance to immune checkpoint blockade","volume":"123","author":"Xiao","year":"2026","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B76","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41392-026-02675-8","article-title":"Short-chain acyl-CoA dehydrogenase initiates mtDNA demethylation and leakage to fuel antitumor immunity in colorectal cancer","volume":"11","author":"Yang","year":"","journal-title":"Signal Transduct. Target. Ther."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.3390\/diagnostics16111582","article-title":"Microbiomics: novel biomarkers of colorectal cancer diagnosis and prognosis","volume":"16","author":"Yang","year":"","journal-title":"Diagnostics"},{"key":"B78","doi-asserted-by":"publisher","first-page":"124085","DOI":"10.1016\/j.biomaterials.2026.124085","article-title":"A manganese-based nanoplatform leveraging chemodynamic and adjuvant effects for in situ vaccination against colorectal cancer","volume":"331","author":"Yang","year":"","journal-title":"Biomaterials"},{"key":"B79","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s11626-024-01000-3","article-title":"OPA3 inhibits the cGAS-STING pathway mediated by mtDNA stress to promote colorectal cancer progression","volume":"61","author":"Yin","year":"2025","journal-title":"In Vitro"},{"key":"B80","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.immuni.2020.05.013","article-title":"Structures and mechanisms in the cGAS-STING innate immunity pathway","volume":"53","author":"Zhang","year":"2020","journal-title":"Immunity"},{"key":"B81","doi-asserted-by":"publisher","first-page":"e010889","DOI":"10.1136\/jitc-2024-010889","article-title":"Selective BCL-2 inhibitor triggers STING-dependent antitumor immunity via inducing mtDNA release","volume":"13","author":"Zhang","year":"","journal-title":"J. Immunother. Cancer"},{"key":"B82","doi-asserted-by":"publisher","first-page":"148421","DOI":"10.1016\/j.ijbiomac.2025.148421","article-title":"Dumbbell-shape DNA structure activates cGAS-STING pathway for enhanced checkpoint immunotherapy in colorectal cancer","volume":"331","author":"Zhang","year":"","journal-title":"Int. J. Biol. Macromol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12967-026-07748-4","article-title":"The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor","volume":"24","author":"Zhao","year":"","journal-title":"J. Transl. Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1186\/s12964-026-02974-1","article-title":"From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment","volume":"24","author":"Zhao","year":"","journal-title":"Cell Commun. Signal."},{"key":"B85","doi-asserted-by":"publisher","first-page":"e012652","DOI":"10.1136\/jitc-2025-012652","article-title":"Targeting VCP enhances colorectal cancer therapy through STING stabilization","volume":"13","author":"Zhu","year":"","journal-title":"J. Immunother. Cancer"},{"key":"B86","doi-asserted-by":"publisher","first-page":"e2500271","DOI":"10.1002\/advs.202500271","article-title":"PRMT5 inhibitor synergizes with chemotherapy to induce resembling mismatch repair deficiency and enhance Anti-TIGIT therapy in microsatellite-stable colorectal cancer","volume":"12","author":"Zhu","year":"","journal-title":"Adv. Sci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/s12276-025-01457-6","article-title":"Cholesterol biosynthesis induced by radiotherapy inhibits cGAS-STING activation and contributes to colorectal cancer treatment resistance","volume":"57","author":"Zhu","year":"","journal-title":"Exp. Mol. Med."},{"key":"B88","doi-asserted-by":"publisher","first-page":"e21146","DOI":"10.1002\/advs.202521146","article-title":"Synergistic activation of immunogenic cell death and the cGAS-STING pathway by engineered Zinc\/manganese-based metal-organic framework nanoplatforms for Colon cancer immunotherapy","volume":"13","author":"Zhu","year":"2026","journal-title":"Adv. Sci."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1939425\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:31:27Z","timestamp":1789101087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1939425\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":88,"alternative-id":["10.3389\/fmolb.2026.1939425"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2026.1939425","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1939425"}}