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The Resistance Mechanisms of Proteasome Inhibitor Bortezomib

Overview
Journal Biomark Res
Publisher Biomed Central
Date 2013 Nov 21
PMID 24252210
Citations 68
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Abstract

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.

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