糖代谢重编程在肿瘤耐药中的研究进展

Advances of glucose metabolic reprogramming in tumor drug resistance

摘要

肿瘤耐药是导致临床治疗失败的主要原因，传统理论认为耐药主要与药物外排增加、DNA修复增强、细胞凋亡抑制等因素有关。近年来越来越多的研究表明，糖代谢重编程作为肿瘤细胞为适应独特的肿瘤微环境、获得生存和增殖优势的关键机制，在调控肿瘤耐药进程中也扮演了非常重要的角色。在为自身快速生长增殖提供持续的物质及能量供应之外，肿瘤细胞异常活跃的有氧糖酵解及磷酸戊糖途径还可以通过调控氧化还原稳态、增强细胞干性、重塑肿瘤微环境等途径影响细胞对药物的耐受性，且将靶向糖代谢重编程与抗肿瘤药物结合的组合疗法已呈现出越来越显著的临床优势。文章对糖代谢重编程在各类抗肿瘤药物耐药中的研究进展进行综述，以期为肿瘤细胞耐药问题日益突出的现状提供全新突破口。

Abstract

Tumor drug resistance is the main cause of clinical treatment failure. According to conventional wisdom，resistance is mostly caused by greater drug efflux，accelerated DNA repair，and decreased apoptosis. In recent years，more and more studies have shown that glucose metabolic reprogramming，as a key mechanism for tumor cells to adapt to the unique tumor microenvironment and obtain the advantages of survival and proliferation，also plays a very important role in regulating the process of tumor drug resistance. In addition to providing sustained material and energy supplies for their own rapid growth and proliferation，the abnormally active aerobic glycolysis and pentose phosphate pathway in tumor cells can also affect drug tolerance through pathways like regulating redox homeostasis，enhancing cellular stemness，and reshaping the tumor microenvironment. Additionally，the combination treatments that target glycose metabolic reprogramming combined with anticancer medications have shown progressively greater therapeutic benefits. This article reviews the research progress of glucose metabolic reprogramming in the resistance to various anti-tumor drugs，in order to provide a new breakthrough for the increasingly prominent status quo of tumor cell drug resistance.

关键词

糖代谢重编程 / 沃伯格效应 / 肿瘤耐药 / 肿瘤微环境 / 代谢组学

Key words

glucose metabolic reprogramming / Warburg effect / tumor drug resistance / tumor microenvironment / metabolomics

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基金资助

江苏省自然科学基金(BK20251962)