{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:04:31Z","timestamp":1791324271779,"version":"4.3.1"},"reference-count":110,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Oral Medicine, Taipei Medical University","award":["TMUCOM202405"],"award-info":[{"award-number":["TMUCOM202405"]}]},{"name":"College of Oral Medicine, Taipei Medical University","award":["ZRRPF6N0011"],"award-info":[{"award-number":["ZRRPF6N0011"]}]},{"name":"Chang Gung University of Science and Technology Foundation","award":["TMUCOM202405"],"award-info":[{"award-number":["TMUCOM202405"]}]},{"name":"Chang Gung University of Science and Technology Foundation","award":["ZRRPF6N0011"],"award-info":[{"award-number":["ZRRPF6N0011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease\u2019s prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin\u2019s ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28\/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin\u2019s application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin\u2019s potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.<\/jats:p>","DOI":"10.3390\/cancers16173017","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:33:37Z","timestamp":1724931217000},"page":"3017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Jui-Hsiang","family":"Li","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yi","family":"Hsin","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Chia","family":"Hsiao","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yun","family":"Zhuang","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiang-Wen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nursing, Division of Basic Medical Sciences, Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan"},{"name":"Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan"},{"name":"Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-9572","authenticated-orcid":false,"given":"Wei-Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Food Safety, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Thuy Tien","family":"Vo","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Fu","family":"Tseng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei 10048, Taiwan"},{"name":"Department of Dentistry, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Fen","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-0280","authenticated-orcid":false,"given":"I-Ta","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11306-023-02038-2","article-title":"Metabolomics of head and neck cancer in biofluids: An integrative systematic review","volume":"19","author":"Chuchueva","year":"2023","journal-title":"Metabolomics"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vincent-Chong, V.K. 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