联合二甲双胍与乳酸转运抑制剂作为癌症治疗方式——推荐建议
Combining metformin with lactate transport inhibitors as a treatment modality for cancer - recommendation proposal.
作者信息
Benjamin Don, Hall Michael N
机构信息
Biozentrum, University of Basel, Basel, Switzerland.
出版信息
Front Oncol. 2022 Oct 24;12:1034397. doi: 10.3389/fonc.2022.1034397. eCollection 2022.
Abstract
Highly glycolytic cancer cells excrete lactate to maintain cellular homeostasis. Inhibiting lactate export by pharmacological targeting of plasma membrane lactate transporters is being pursued as an anti-cancer therapy. Work from many laboratories show that the simultaneous inhibition of lactate export and mitochondrial respiration elicits strong synthetic lethality. The mitochondrial inhibitor, metformin, has been the subject of numerous clinical trials as an anti-cancer agent. We propose that, in future clinical trials, metformin be combined with lactate transport inhibitors to exploit this synergistic interaction.
摘要
高度糖酵解的癌细胞会分泌乳酸以维持细胞内稳态。通过对质膜乳酸转运体进行药理学靶向抑制乳酸输出，正被作为一种抗癌疗法进行研究。许多实验室的研究表明，同时抑制乳酸输出和线粒体呼吸会引发强烈的合成致死效应。线粒体抑制剂二甲双胍作为一种抗癌药物，已经进行了大量的临床试验。我们建议，在未来的临床试验中，将二甲双胍与乳酸转运抑制剂联合使用，以利用这种协同相互作用。
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