蛋白酶体抑制剂治疗多发性骨髓瘤的研究进展

Research progress of proteasome inhibitors in treatment of multiple myeloma

目前，多发性骨髓瘤（MM）在血液系统恶性肿瘤中发病比例较高，其患病率亦逐年升高。近年来，蛋白酶体抑制剂（PI）的出现使MM的治疗有了革命性突破。PI通过抑制蛋白酶体降解相关蛋白，使细胞内泛素化蛋白和（或）错误折叠的蛋白积累，导致细胞凋亡。不同PI的作用机制不尽相同，其在抗肿瘤过程中产生的疗效和药物不良反应亦不同。因此，深入了解各种PI的作用机制、疗效及安全性，能更好为临床抗MM的药物选择提供理论依据。笔者主要阐述PI治疗MM的相关研究进展及临床应用。

Multiple myeloma（MM） cases constitute a relatively high proportion of patients suffering from hematological malignant diseases, with its prevalence rate mounting every year. Substantial breakthrough of MM treatment has been achieved due to the development of proteasome inhibitors（PI）, which facilitates cellular apoptosis induced by the accumulation of intracellular ubiquitinated and/or misfolded proteins, via the inhibition of the degradation of the apoptosis-associated proteins. The exact pharmaceutical mechanisms of different PI vary, leading to different therapeutic effects and drug adverse reactions. Further understanding of the pharmaceutical mechanisms, therapeutic effects and safety of various PI lays the theoretical foundation for their clinical use. This article focuses the research progress and the clinical application of PIs in terms of MM treatment.