Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Trends Cancer. 2021 Aug;7(8):714-730. doi: 10.1016/j.trecan.2021.03.001. Epub 2021 Apr 14.
Biguanides are a class of antidiabetic drugs that includes phenformin and metformin; however, the former was withdrawn from approval in many countries due to its toxicity.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.
双胍类药物是一类抗糖尿病药物，包括苯乙双胍和二甲双胍；然而，由于其毒性，前者已在许多国家被撤回批准。糖尿病患者的回顾性流行病学研究和临床前实验室模型的结果表明，双胍类药物具有抗肿瘤活性，提示它们可重新用于癌症的预防和治疗。然而，需要更好地了解这些双胍类药物作为抗肿瘤药物的作用方式，以指导它们在癌症治疗中的应用，这促使人们对其药理学产生了更大的兴趣。在这里，我们提出了与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中心碳代谢的影响和免疫调节活性，然后综述了双胍类药物在癌症治疗中的重新应用以及重新评估苯乙双胍作为癌症治疗剂的可能性方面的进展。
