Cumming School of Medicine, University of Calgary, 1403, 29th Street NW, Calgary, T2N2T9, AB, Canada.
Cell Oncol (Dordr). 2021 Feb;44(1):1-18. doi: 10.1007/s13402-020-00570-0. Epub 2020 Oct 30.
Metformin, a first-line therapeutic for type 2 diabetes, has been studied for its potential use in cancer treatment following a number of epidemiological studies that have demonstrated reduced cancer incidence and mortality rates among patients treated with the drug. As yet, however, there remains significant uncertainty about the molecular mechanisms by which metformin exerts its anti-cancer effects. Herein, we summarize the evidence surrounding the anti-lung cancer effects of metformin.
Specifically, we explore protein targets of metformin, including AMPK, PP2A, IRF-1/YAP and HGF and we outline the proposed mechanisms of action for metformin in lung cancer, with particular attention given to apoptosis and autophagy. We also closely examine the synergistic activity of metformin with existing cancer treatment regimens, such as TKI's, platinum-based agents and immune therapeutics. In addition to considering preclinical and clinical studies, we also dissect and contextualize the limitations and inconsistencies of the current literature, especially those of epidemiological studies. Finally, we offer a potential trajectory for future research in this rapidly evolving area of basic and clinical oncology.
二甲双胍是治疗 2 型糖尿病的一线药物，一些流行病学研究表明，接受该药治疗的患者癌症发病率和死亡率降低，此后，人们对二甲双胍发挥抗癌作用的分子机制仍存在很大的不确定性。在此，我们总结了二甲双胍在肺癌方面的抗癌作用的证据。
具体而言，我们探讨了二甲双胍的蛋白靶标，包括 AMPK、PP2A、IRF-1/YAP 和 HGF，并概述了二甲双胍在肺癌中的作用机制，特别关注凋亡和自噬。我们还仔细研究了二甲双胍与现有癌症治疗方案（如 TKI、铂类药物和免疫疗法）的协同作用。除了考虑临床前和临床研究外，我们还剖析并厘清了当前文献的局限性和不一致性，尤其是流行病学研究的局限性和不一致性。最后，我们为这一快速发展的基础和临床肿瘤学领域的未来研究提供了一个潜在的方向。
