School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, E. 232, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, China; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China.
Department of Pharmaceutical Production Center, The First Hospital of Hunan University of Chinese Medicine, 95, Shaoshan Rd, Changsha, Hunan, 41007, China.
Eur J Med Chem. 2021 Aug 5;220:113487. doi: 10.1016/j.ejmech.2021.113487. Epub 2021 Apr 23.
Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells readily emerge after long exposure to chemotherapeutics drugs, resulting in multi-drug resistance (MDR) and treatment failure. Recently, growing evidences indicate that the molecular action mechanisms of cancer MDR are closely associated with abnormalities in saccharides. In this review, saccharides affecting cancer MDR development are elaborated and analyzed in terms of aberrant aerobic glycolysis and its related enzymes, abnormal glycan structures and their associated enzymes, and glycoproteins. The reversal strategies including depletion of ATP, circumventing the original MDR pathway, activation by or inhibition of sugar-related enzymes, combination therapy with traditional cytotoxic agents, and direct modification on the sugar moiety, are ultimately proposed. It follows that abnormal saccharides have a significant effect on cancer MDR development, providing a new perspective for overcoming MDR and improving the outcome of chemotherapy.
临床上,化疗是多种癌症治疗的主要手段。然而,癌细胞经过长期接触化疗药物后,很容易出现高度适应和激活的存活信号通路,导致多药耐药(MDR)和治疗失败。最近,越来越多的证据表明,癌症 MDR 的分子作用机制与糖的异常密切相关。在这篇综述中,阐述和分析了影响癌症 MDR 发展的糖,包括异常的有氧糖酵解及其相关酶、异常的糖链结构及其相关酶和糖蛋白。最终提出了逆转策略,包括耗尽 ATP、绕过原始 MDR 途径、糖相关酶的激活或抑制、与传统细胞毒药物联合治疗以及对糖部分的直接修饰。因此,异常的糖对癌症 MDR 的发展有显著影响,为克服 MDR 和提高化疗效果提供了新的视角。