Background

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.

Conclusions

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.

中文翻译：

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强调二甲双胍作为肺癌治疗剂作用的分子机制

背景

二甲双胍是 2 型糖尿病的一线治疗药物，在多项流行病学研究表明该药物治疗的患者中癌症发病率和死亡率降低后，已经对其在癌症治疗中的潜在用途进行了研究。然而，到目前为止，二甲双胍发挥抗癌作用的分子机制仍然存在很大的不确定性。在此，我们总结了有关二甲双胍抗肺癌作用的证据。

结论

具体而言，我们探索了二甲双胍的蛋白质靶标，包括 AMPK、PP2A、IRF-1/YAP 和 HGF，并概述了二甲双胍在肺癌中的拟议作用机制，特别关注细胞凋亡和自噬。我们还仔细研究了二甲双胍与现有癌症治疗方案（例如 TKI、铂类药物和免疫疗法）的协同活性。除了考虑临床前和临床研究外，我们还剖析了当前文献的局限性和不一致之处，尤其是流行病学研究的局限性和不一致之处。最后，我们为这个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轨迹。