A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.

Simple Summary: Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a widespread health problem with limited treatment options and poor survival rates. Metformin, a common medication for managing diabetes, has recently shown promise as a potential treatment for various cancers, including OSCC. This review examines the potential benefits of repurposing metformin to treat oral cancer. Studies have shown that metformin can reduce the growth of cancer cells, induce cancer cell death, and improve the effectiveness of existing treatments. It works by affecting several pathways involved in cancer development, such as those related to cell energy and inflammation. However, using metformin for cancer treatment comes with challenges, including possible side effects and interactions with other medications. More research and clinical trials are needed to understand how metformin can be effectively used in cancer treatment and to ensure its safety. If proven effective, metformin could provide a new, cost-effective option for treating oral cancer, potentially improving outcomes and quality of life for patients. 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's 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's 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's 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's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies. [ABSTRACT FROM AUTHOR]