Biguanides are a class of antidiabetic drugs that includes phenformin and metformin; however, the former was withdrawn from approval in many countries due to its toxicity. Findings from retrospective epidemiological studies in diabetic populations and preclinical laboratory models have demonstrated that biguanides possess antitumor activities that suggest their repurposing for cancer prevention and treatment. However, a better understanding of how these biguanides behave as antitumor agents is needed to guide their improved applications in cancer therapy, spurring increased interest in their pharmacology. Here, we present evidence for proposed mechanisms of action related to their antitumor activity, including their effects on central carbon metabolism in cancer cells and immune-modulating activity, and then review progress on biguanide repurposing in cancer therapeutics and the possible re-evaluation of phenformin as a cancer therapeutic agent.

双胍类是一类抗糖尿病药物，包括苯二甲双胍和二甲双胍；然而，前者因其毒性而在许多国家被撤回批准。对糖尿病人群和临床前实验室模型的回顾性流行病学研究结果表明，双胍具有抗肿瘤活性，表明它们可重新用于癌症预防和治疗。然而，需要更好地了解这些双胍类作为抗肿瘤剂的作用，以指导它们在癌症治疗中的改进应用，从而激发人们对其药理学的兴趣。在这里，我们提出了与其抗肿瘤活性相关的拟议作用机制的证据，包括它们对癌细胞中枢碳代谢和免疫调节活性的影响，