腫瘤細(xì)胞的代謝重編程是癌癥發(fā)生和發(fā)展的重要特征。通過(guò)調(diào)控代謝途徑，腫瘤細(xì)胞能夠滿足快速增殖的需求，其中糖酵解和磷酸戊糖途徑（PPP）是2條關(guān)鍵的代謝途徑。近期研究發(fā)現(xiàn)，糖酵解與PPP之間存在復(fù)雜的代謝串?dāng)_，腫瘤細(xì)胞通過(guò)調(diào)節(jié)兩條途徑的交叉點(diǎn)，如葡萄糖-6-磷酸（G6P）和果糖-6-磷酸（F6P），靈活調(diào)整代謝通量以適應(yīng)腫瘤微環(huán)境的變化。這些代謝交叉點(diǎn)不僅揭示了腫瘤細(xì)胞代謝的復(fù)雜性，也為靶向藥物的開(kāi)發(fā)提供了新的方向。當(dāng)前，針對(duì)這些代謝交叉點(diǎn)的靶向藥物研究取得了積極進(jìn)展，抑制葡萄糖-6-磷酸脫氫酶（G6PD）和轉(zhuǎn)酮醇酶（TKT）的藥物已顯示出良好的抗腫瘤效果。此外，一些中藥活性成分也顯示出可調(diào)節(jié)糖酵解和PPP來(lái)增強(qiáng)化療藥物的療效，這為聯(lián)合用藥提供了新的思路。因此，深入探索糖酵解與PPP之間的串?dāng)_機(jī)制及其在癌癥治療中的應(yīng)用，將為靶向藥物的開(kāi)發(fā)和現(xiàn)有治療策略的優(yōu)化提供重要的理論依據(jù)和實(shí)踐指導(dǎo)。重點(diǎn)討論這些代謝交叉點(diǎn)的生物學(xué)意義，以及靶向這些代謝途徑交叉點(diǎn)的藥物開(kāi)發(fā)現(xiàn)狀，探討其在癌癥治療中的潛力與挑戰(zhàn)。

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

天津市自然科學(xué)基金項(xiàng)目（23JCZXJC00150、23JCJQJC00040）