蛋白酶体抑制剂硼替佐米在多发性骨髓瘤中的耐药机制

Mechanism of resistance to proteasome inhibitor bortezomib in multiple myeloma

多发性骨髓瘤（MM）是好发于老年人的恶性浆细胞疾病。近年来，小分子蛋白酶体抑制剂和免疫调节剂（IMiD）的应用，使MM从一种缺乏有效治疗手段的致死性疾病转变成对新型治疗反应良好的慢性疾病。然而，耐药的发生使MM仍不可治愈，这已成为当前MM临床治疗的最大挑战之一。文章对硼替佐米在MM治疗中的获得性耐药机制进行综述，主要包括靶基因修饰、旁路信号等机制。

Multiple myeloma （MM） is a malignant plasma cell disease which occured predominantly in the elderly. In recent years, due to the application of small molecular proteasome inhibitor and immunomodulator, MM has become a chronic disease with good response to new treatments rather than a deadly disease that is lack of effective treatments. However, the occurrence of drug resistance makes MM less likely to be cured, which is one of the biggest challenges in MM clinical treatment. This article will review the mechanisms of acquired resistance to bortezomib in MM, including target genes modification, bypass signaling and so forth.