{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:09:45Z","timestamp":1768525785846,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,4]]},"group-title":"Cancer Biology","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T00:00:00Z","timestamp":1759536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA193522"],"award-info":[{"award-number":["R01CA193522"]}]},{"name":"National Cancer Institute","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}]},{"name":"National Cancer Institute","award":["P30CA034196"],"award-info":[{"award-number":["P30CA034196"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cancer-related inflammation and metabolic alterations extend beyond the tumor microenvironment, exerting systemic effects that disrupt energy homeostasis and contribute to reduced physical function and chronic fatigue. The cGAS\u2013STING pathway has emerged as a key regulator of innate immunity and inflammation; however, its role in cancer-associated fatigue remains poorly understood. In this study, we investigated the contribution of cGAS\u2013 STING\u2013mediated inflammation to cancer- and\/or its treatment-induced fatigue using a mouse model of human papillomavirus-related head and neck cancer. Wheel running activity, along with inflammatory and metabolic changes in tumor and liver tissues, were assessed following chemoradiotherapy and pharmacological inhibition of STING in tumor-bearing and tumor-free control mice. The results revealed that tumor growth and chemoradiotherapy activated the cGAS-STING pathway, together with an upregulation of proinflammatory mediators and alterations of mitochondrial and metabolic gene expression in the liver. To inhibit STING activation, mice were administered H-151, a specific STING antagonist. This intervention attenuated hepatic inflammatory signatures and mitigated tumor and\/or chemoradiotherapy-associated behavioral fatigue measured by decreased voluntary wheel running. These findings implicate for the first time the cGAS\u2013STING signaling pathway and metabolic homeostasis in cancer- and cancer therapy-related fatigue.<\/jats:p>","DOI":"10.1101\/2025.10.02.680158","type":"posted-content","created":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T05:05:11Z","timestamp":1759640711000},"source":"Crossref","is-referenced-by-count":0,"title":["Activation of the cGAS-STING pathway contributes to cancer-related fatigue in a murine model of head and neck cancer"],"prefix":"10.64898","author":[{"given":"Brandon","family":"Chelette","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abate","family":"Bashaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua D.","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiersten","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinenye","family":"Chidomere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2884-6895","authenticated-orcid":false,"given":"A. 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