Progress in antitumor mechanisms and applications of phenformin (Review)

Phenformin, a biguanide compound, has attracted increased attention due to its prominent antitumor activity. As a multi-target agent, the antitumor effects of phenformin involve a wide range of factors, including inhibition of mitochondrial complex I, activation of AMP-activated protein kinase, impact on the tumor microenvironment, suppression of cancer stem cells and others. In addition, phenformin has been shown to markedly augment the effectiveness of various clinical treatment methods, including radiotherapy, chemotherapy, targeted therapy and immunotherapy. It is noteworthy that breakthrough progress has been made in the treatment of cancer with phenformin with application in clinical trials for the treatment of melanoma. Phenformin not only reduces the lesion area of patients, but also enhances the efficacy of dalafinib/trimetinib. In the present review, the novel breakthroughs in the antitumor effects and mechanisms of phenformin were discussed. In addition, the current review focuses on the clinical development value of phenformin, striving to provide new insights into the future research direction of phenformin in the field of tumor treatment.