Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy
Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy
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DOI：
10.1016/j.phrs.2019.104511
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发表时间：
2019-12-01
影响因子：
9.3
通讯作者：
Al-Harizy, Randa M.
中科院分区：
文献类型：
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作者：
Abdel-Wahab, Ali F.;Mahmoud, Waheed;Al-Harizy, Randa M.
大多数实体瘤细胞通过在很大程度上依赖有氧糖酵解来产生能量来适应其异质性微环境，这种现象称为瓦尔堡效应，这是癌症的标志。改变的能量代谢不仅为癌细胞提供细胞能量的ATP，而且还产生在大分子生物合成中起关键作用的必需代谢中间体，以支持细胞增殖、侵袭性和化学抗性。肿瘤中的细胞代谢重编程受多种致癌蛋白和肿瘤抑制因子如缺氧诱导因子（HIF-1）、Myc、p53和PI 3 K/Akt/mTOR通路的调节。更好地了解有氧糖酵解调节机制有助于开发糖酵解抑制剂作为抗癌药物。这些代谢性抗糖酵解剂如果用于药物组合来对抗癌症可能会更有效。一些临床前和早期临床研究已经显示了靶向糖酵解途径作为抑制癌症进展的治疗方法的有效性。本文综述了近年来以糖代谢相关酶和中间体为靶点的新型抗癌药物的最新研究进展，为抗糖酵解肿瘤治疗提供了新的机遇和挑战。
Most solid tumor cells adapt to their heterogeneous microenvironment by depending largely on aerobic glycolysis for energy production, a phenomenon called the Warburg effect, which is a hallmark of cancer. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generate essential metabolic intermediates that play a pivotal role in the biosynthesis of macromolecules, to support cell proliferation, invasiveness, and chemoresistance. The cellular metabolic reprogramming in cancer is regulated by several oncogenic proteins and tumor suppressors such as hypoxia-inducible factor (HIF-1), Myc, p53, and PI3K/Akt/mTOR pathway. A better understanding of the mechanisms involved in the regulation of aerobic glycolysis can help in developing glycolytic inhibitors as anticancer agents. These metabolic antiglycolytic agents could be more effective if used in drug combinations to combat cancer. Several preclinical and early clinical studies have shown the effectiveness of targeting the glycolytic pathway as a therapeutic approach to suppress cancer progression. This review aimed to present the most recent data on the emerging drug candidate targeting enzymes and intermediates involved in glucose metabolism to provide therapeutic opportunities and challenges for antiglycolytic cancer therapy.