A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake and consumption of glucose. The Warburg effect may be exploited in the treatment of cancer; certain epimers and derivatives of glucose can enter cancer cells and inhibit glycolytic enzymes, stunting metabolism and causing cell death. These include common dietary monosaccharides (ᴅ-mannose, ᴅ-galactose, ᴅ-glucosamine, ʟ-fucose), as well as some rare monosaccharides (xylitol, ᴅ-allose, ʟ-sorbose, ʟ-rhamnose). This article reviews the literature on these sugars in in vitro and in vivo models of cancer, discussing their mechanisms of cytotoxicity. In addition to this, the anticancer potential of some synthetically modified monosaccharides, such as 2-deoxy-ᴅ-glucose and its acetylated and halogenated derivatives, is reviewed. Further, this article reviews how certain monosaccharides can be used in combination with anticancer drugs to potentiate conventional chemotherapies and to help overcome chemoresistance. Finally, the limitations of administering two separate agents, a sugar and a chemotherapeutic drug, are discussed. The potential of the glycoconjugation of classical or repurposed chemotherapy drugs as a solution to these limitations is reviewed.
癌症的一个主要特征是细胞代谢从氧化磷酸化（OXPHOS）重编程为糖酵解，这一现象被称为瓦博格效应。为维持高糖酵解速率，癌细胞过度表达GLUT转运蛋白和糖酵解酶，从而增强葡萄糖的摄取和消耗。瓦博格效应可用于癌症治疗；某些葡萄糖的差向异构体和衍生物可进入癌细胞并抑制糖酵解酶，阻碍代谢并导致细胞死亡。这些物质包括常见的膳食单糖（ᴅ-甘露糖、ᴅ-半乳糖、ᴅ-葡萄糖胺、ʟ-岩藻糖）以及一些稀有单糖（木糖醇、ᴅ-阿洛糖、ʟ-山梨糖、ʟ-鼠李糖）。本文综述了这些糖类在体外和体内癌症模型中的相关文献，探讨了其细胞毒性机制。此外，还综述了部分合成修饰单糖（如2-脱氧-ᴅ-葡萄糖及其乙酰化和卤化衍生物）的抗癌潜力。进一步地，本文探讨了某些单糖如何与抗癌药物联用以增强传统化疗效果并帮助克服化疗耐药性。最后，讨论了分别施用糖类与化疗药物两种独立制剂存在的局限性，并综述了将经典化疗药物或老药新用药物进行糖基化偶联作为解决这些局限性的潜在方案。
The Anticancer Activity of Monosaccharides: Perspectives and Outlooks
肿瘤(癌症)患者之家