Department of Hematology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
Biomark Res. 2013 Mar 1;1(1):13. doi: 10.1186/2050-7771-1-13.
The proteasome inhibitor, bortezomib, a boronic dipeptide which reversibly inhibit the chymotrypsin-like activity at the β5-subunit of proteasome (PSMB5), has marked efficacy against multiple myeloma and several non-Hodgkin's lymphoma subtypes, and has a potential therapeutic role against other malignancy diseases. However, intrinsic and acquired resistance to bortezomib may limit its efficacy. In this article, we discuss recent advances in the molecular understanding of bortezomib resistance. Resistance mechanisms discussed include mutations of PSMB5 and the up-regulation of proteasome subunits, alterations of gene and protein expression in stress response, cell survival and antiapoptotic pathways, and multidrug resistance.
蛋白酶体抑制剂硼替佐米是一种硼酸二肽化合物,可可逆地抑制蛋白酶体(PSMB5)β5 亚基的糜蛋白酶样活性,对多发性骨髓瘤和几种非霍奇金淋巴瘤亚型具有显著疗效,并可能对其他恶性肿瘤疾病具有治疗作用。然而,硼替佐米的内在和获得性耐药可能限制其疗效。本文讨论了对硼替佐米耐药的分子机制的最新研究进展。讨论的耐药机制包括 PSMB5 突变和蛋白酶体亚基的上调、应激反应、细胞存活和抗凋亡途径中的基因和蛋白表达的改变以及多药耐药。