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Biomarker Research

, 1:13

First Online: 01 March 2013Received: 24 November 2012Accepted: 02 February 2013DOI: 10.1186-2050-7771-1-13

Cite this article as: Lü, S. & Wang, J. Biomark Res 2013 1: 13. doi:10.1186-2050-7771-1-13

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.

KeywordsDrug resistance Mechanism Proteasome inhibitor Bortezomib PSMB5 AbbreviationsPSMB5β5-subunit of proteasome

MMMultiple myeloma

NF-κBNuclear factor-κB

P-gpP-glycoprotein

MDRMultidrug resistance

HSPsHeat shock proteins:HSPs

IL-6Interleukin-6

IGF-1Insulin-like growth factor 1

IGF-1RInsulin-like growth factor 1 receptor

5-HAQ5-amino-8-hydroxyquinoline

NSCLCNon-small cell lung cancer

EREndoplasmic reticulum, DNR: daunorubicin.

Electronic supplementary materialThe online version of this article doi:10.1186-2050-7771-1-13 contains supplementary material, which is available to authorized users.

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Author: Shuqing Lü - Jianmin Wang

Source: https://link.springer.com/



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