Repurposing Metformin in Precision Oncology: Mechanistic Insights, Biomarker-Guided Strategies, and Translational Imperatives

Background and Objectives: Metformin, a staple in diabetes care, has recently emerged as a candidate chemotherapeutic agent. In vitro studies suggest that metformin inhibits cancer growth by altering cellular metabolism and enhancing immune responses. Clinical observations further indicate that it suppresses key tumor-promoting pathways such as mTOR and STAT3. This review critically evaluates the therapeutic potential of metformin in oncology through the lens of precision medicine. This review integrates evidence from molecular mechanisms, clinical studies, biomarker-driven trial designs, and the regulatory challenges that continue to delay its approval for oncologic use. Methods: A structured literature search (2015–2025) identified 63 relevant studies, including preclinical, clinical, and translational research. Conclusions: Although metformin shows consistent anticancer effects in laboratory and animal models, its clinical benefits in patients are variable. This inconsistency is likely due to tumor heterogeneity and a lack of biomarker-based patient selection in trials. Targeting these shortcomings through biomarker-enriched, tumor-specific clinical trials is essential to define metformin’s role as a repurposed agent in precision oncology.