Multiple myeloma is a hematological malignancy that has evolved from antibody-secreting B lymphocytes. Like other types of cancers, myeloma cells have acquired functional capabilities which are referred to as “Hallmarks of Cancer”, and one of their most important features is the metabolic disorders. Due to the high secretory load of the MM cells, the first-line medicine proteasome inhibitors have found their pronounced effects in MM cells for blocking the degradation of misfolded proteins, leading to their accumulation in the ER and overwhelming ER stress. Moreover, proteasome inhibitors have been reported to be effective in myeloma by targeting glucose, lipid, amino acid metabolism of MM cells. In this review, we have described the abnormal metabolism of the three major nutrients, such as glucose, lipid and amino acids, which participate in the cellular functions. We have described their roles in myeloma progression, how they could be exploited for therapeutic purposes, and current therapeutic strategies targeting these metabolites, hoping to uncover potential novel therapeutic targets and promote the development of future therapeutic approaches.

中文翻译：

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靶向骨髓瘤代谢：代谢异常如何导致多发性骨髓瘤进展和对蛋白酶体抑制剂的耐药性

多发性骨髓瘤是一种血液恶性肿瘤，由分泌抗体的 B 淋巴细胞演变而来。与其他类型的癌症一样，骨髓瘤细胞已获得被称为“癌症标志”的功能能力，其中最重要的特征之一是代谢紊乱。由于MM细胞的高分泌负荷，一线药物蛋白酶体抑制剂在MM细胞中发现其显着的作用，可以阻止错误折叠蛋白的降解，从而导致它们在ER中积累并产生压倒性的ER应激。此外，据报道，蛋白酶体抑制剂通过靶向多发性骨髓瘤细胞的葡萄糖、脂质、氨基酸代谢，对骨髓瘤有效。在这篇综述中，我们描述了参与细胞功能的三大营养素（例如葡萄糖、脂质和氨基酸）的异常代谢。我们描述了它们在骨髓瘤进展中的作用、如何将它们用于治疗目的以及当前针对这些代谢物的治疗策略，希望发现潜在的新治疗靶点并促进未来治疗方法的发展。