许多癌症患者仍然缺乏有效治疗，而现有或获得性耐药性则限制了即使是最先进的药物的临床效益。最近，人们对代谢在癌症中的作用给予了很多关注，从沃尔堡效应拓展到突出显示出的独特模式，进而可以改善诊断和治疗方法。我们最近的代谢组学研究揭示了利比通能够改变乳腺癌细胞中的糖酵解。在当前研究中，我们研究了利比通与几种其他抗癌药物（染黄素、洛尼达胺、GSK2837808A、CB-839、JQ1和赤芪酮）在不同的乳腺癌细胞（MDA-MB-231、MCF-7和T-47D）中的联合作用。利比通与JQ1的联合作用在抑制乳腺癌细胞的增殖和迁移方面显示出协同作用，且与细胞类型依赖有关，仅在三阴性MDA-MB-231乳腺癌细胞中观察到。这种协同作用与两种化合物对细胞存活与死亡相关基因表达的差异效应有关，特别是c-Myc和其他抗凋亡蛋白（Bcl-2、Bcl-xL、Mcl-1）的下调，以及p53和细胞色素C水平的上调。糖酵解发生了差异性改变，利比通和JQ1分别显著下调了葡萄糖-6-磷酸和乳酸。联合治疗对代谢和凋亡相关基因的整体影响导致细胞生长的显著协同抑制和凋亡诱导。鉴于利比通是一种副作用有限的代谢产物，与其他药物联合治疗在临床上治疗适宜的癌症人群上易于应用，因此非常理想。我们的研究结果还强调，类似于传统药物开发，以代谢为靶点治疗癌症的治疗潜力可能仅能通过与其他药物的联合使用实现，并需要识别特定的癌症人群。将代谢组学干预应用于大范围的癌症类型的愿望，可能是临床试验中识别此类药物的原因之一被延迟。

Many cancer patients still lack effective treatments, and pre-existing or acquired resistance limits the clinical benefit of even the most advanced medicines. Recently, much attention has been given to the role of metabolism in cancer, expanding from the Warburg effect to highlight unique patterns that, in turn, may improve diagnostic and therapeutic approaches. Our recent metabolomics study revealed that ribitol can alter glycolysis in breast cancer cells. In the current study, we investigate the combinatorial effects of ribitol with several other anticancer drugs (chrysin, lonidamine, GSK2837808A, CB-839, JQ1, and shikonin) in various breast cancer cells (MDA-MB-231, MCF-7, and T-47D). The combination of ribitol with JQ1 synergistically inhibited the proliferation and migration of breast cancer cells cell-type dependently, only observed in the triple-negative MDA-MB-231 breast cancer cells. This synergy is associated with the differential effects of the 2 compounds on expression of the genes involved in cell survival and death, specifically downregulation in c-Myc and other anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1), but upregulation in p53 and cytochrome C levels. Glycolysis is differentially altered, with significant downregulation of glucose-6-phosphate and lactate by ribitol and JQ1, respectively. The overall effect of the combined treatment on metabolism and apoptosis-related genes results in significant synergy in the inhibition of cell growth and induction of apoptosis. Given the fact that ribitol is a metabolite with limited side effects, a combined therapy is highly desirable with relative ease to apply in the clinic for treating an appropriate cancer population. Our results also emphasize that, similar to traditional drug development, the therapeutic potential of targeting metabolism for cancer treatment may only be achieved in combination with other drugs and requires the identification of a specific cancer population. The desire to apply metabolomic intervention to a large scope of cancer types may be one of the reasons identification of this class of drugs in a clinical trial setting has been delayed.