Journal
BIOMARKER RESEARCH
Volume 1, Issue -, Pages -Publisher
BMC
DOI: 10.1186/2050-7771-1-13
Keywords
Drug resistance; Mechanism; Proteasome inhibitor; Bortezomib; PSMB5
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Funding
- National Natural Science Foundation of China [30873042, 81100361]
- Shanghai Natural Science Foundation of Shanghai Science and Technology Committee, China [07ZR14146]
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The proteasome inhibitor, bortezomib, a boronic dipeptide which reversibly inhibit the chymotrypsin-like activity at the beta 5-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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