The resistance mechanisms of proteasome inhibitor bortezomib.
The resistance mechanisms of proteasome inhibitor bortezomib.
复制标题
蛋白酶体抑制剂硼替佐米的耐药机制
DOI：
10.1186/2050-7771-1-13
复制
发表时间：
2013-03-01
影响因子：
11.1
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Lü S;Wang J
蛋白酶体抑制剂Bortezomib是一种能可逆地抑制蛋白酶体β5亚单位的凝乳酶样活性的硼酸二肽，对多发性骨髓瘤和几种非霍奇金淋巴瘤亚型有显著的疗效，并对其他恶性肿瘤具有潜在的治疗作用。然而，对Bortezomib的内在和获得性耐药性可能会限制其疗效。在这篇文章中，我们讨论了波特佐米耐药性的分子理解的最新进展。耐药机制包括PSMB5基因突变和蛋白酶体亚基上调、应激反应中基因和蛋白表达的改变、细胞存活和抗凋亡途径以及多药耐药。
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.