肿瘤细胞的代谢重编程是癌症发生和发展的重要特征。通过调控代谢途径，肿瘤细胞能够满足快速增殖的需求，其中糖酵解和磷酸戊糖途径（PPP）是2条关键的代谢途径。近期研究发现，糖酵解与PPP之间存在复杂的代谢串扰，肿瘤细胞通过调节两条途径的交叉点，如葡萄糖-6-磷酸（G6P）和果糖-6-磷酸（F6P），灵活调整代谢通量以适应肿瘤微环境的变化。这些代谢交叉点不仅揭示了肿瘤细胞代谢的复杂性，也为靶向药物的开发提供了新的方向。当前，针对这些代谢交叉点的靶向药物研究取得了积极进展，抑制葡萄糖-6-磷酸脱氢酶（G6PD）和转酮醇酶（TKT）的药物已显示出良好的抗肿瘤效果。此外，一些中药活性成分也显示出可调节糖酵解和PPP来增强化疗药物的疗效，这为联合用药提供了新的思路。因此，深入探索糖酵解与PPP之间的串扰机制及其在癌症治疗中的应用，将为靶向药物的开发和现有治疗策略的优化提供重要的理论依据和实践指导。重点讨论这些代谢交叉点的生物学意义，以及靶向这些代谢途径交叉点的药物开发现状，探讨其在癌症治疗中的潜力与挑战。

Metabolic reprogramming of tumor cells is an important feature of cancer development and progression. By regulating metabolic pathways, tumor cells are able to meet the demands of rapid proliferation, of which glycolysis and the pentose phosphate pathway (PPP) are two key metabolic pathways. Recent studies have revealed a complex metabolic crosstalk between glycolysis and PPP. Tumor cells flexibly adjust their metabolic fluxes to adapt to the changes in the tumor microenvironment by regulating the intersection of the two pathways, such as glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P). These metabolic crossroads not only reveal the complexity of tumor cell metabolism, but also provide new directions for targeted drug development. Currently, the research on targeted drugs against these metabolic crossroads has made positive progress, and drugs inhibiting G6P dehydrogenase (G6PD) and transketolase (TKT) have shown good anti-tumor effects. In addition, some active ingredients of traditional Chinese medicine have been shown to modulate glycolysis and PPP to enhance the efficacy of chemotherapeutic drugs, which provides a new idea for the combination of drugs. Therefore, in-depth exploration of the crosstalk mechanism between glycolysis and PPP and its application in cancer therapy will provide an important theoretical basis and practical guidance for the development of targeted drugs and the optimization of existing therapeutic strategies. In this paper, we will focus on the biological significance of these metabolic crossovers and the current status of drug development targeting these metabolic pathway crossovers to explore their potential and challenges in cancer therapy

R979.1

天津市自然科学基金项目（23JCZXJC00150、23JCJQJC00040）