From basics to clinics: New opportunities for metformin in tumor metabolic intervention and treatment

Abstract

Metformin, a cornerstone therapy for type 2 diabetes, has recently garnered attention for its multifaceted antitumor potential in cancer prevention and treatment. Emerging preclinical studies reveal that metformin suppresses tumor growth and metastasis through integrated mechanisms beyond singular metabolic pathways, while enhancing sensitivity to immunotherapy. Clinical evidence preliminarily supports its survival benefits and risk reduction in breast, colorectal, and hepatocellular carcinomas, particularly when combined with conventional or novel anticancer agents, demonstrating synergistic efficacy. Epidemiological and real-world data further highlight its preventive value in high-risk populations. Despite heterogeneity in therapeutic responses across cancer types and individuals, as well as unresolved challenges in long-term safety and acquired resistance, innovative drug delivery systems and precision oncology approaches are expanding its therapeutic boundaries. Bridging mechanistic insights with clinical translation, metformin is poised to emerge as a pivotal agent in metabolic-immunological synergy, offering novel paradigms for personalized cancer interception and therapy. This review systematically deciphers metformin’s pleiotropic mechanisms in cancer metabolism and anti-tumor immunity while critically evaluating its translational prospects, thereby illuminating new avenues for combinatorial metabolic-immunotherapeutic strategies.