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Targeting the UPS as therapy in multiple myeloma

The coordinated regulation of cellular protein synthesis and degradation is essential for normal cellular functioning. The ubiquitin proteasome system mediates the intracellular protein degradation that is required for normal cellular homeostasis. The 26S proteasome is a multi-enzyme protease that d...

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Detalles Bibliográficos
Autores principales: Chauhan, Dharminder, Bianchi, Giada, Anderson, Kenneth C
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582802/
https://www.ncbi.nlm.nih.gov/pubmed/19007431
http://dx.doi.org/10.1186/1471-2091-9-S1-S1
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author Chauhan, Dharminder
Bianchi, Giada
Anderson, Kenneth C
author_facet Chauhan, Dharminder
Bianchi, Giada
Anderson, Kenneth C
author_sort Chauhan, Dharminder
collection PubMed
description The coordinated regulation of cellular protein synthesis and degradation is essential for normal cellular functioning. The ubiquitin proteasome system mediates the intracellular protein degradation that is required for normal cellular homeostasis. The 26S proteasome is a multi-enzyme protease that degrades redundant proteins; conversely, inhibition of proteasomal degradation results in intracellular aggregation of unwanted proteins and cell death. This observation led to the development of proteasome inhibitors as therapeutics for use in cancer. The clinical applicability of targeting proteasomes is exemplified by the recent FDA approval of the first proteasome inhibitor, bortezomib, for the treatment of relapsed/refractory multiple myeloma. Although bortezomib represents a major advance in the treatment of this disease, it can be associated with toxicity and the development of drug resistance. Importantly, extensive preclinical studies suggest that combination therapies can both circumvent drug resistance and reduce toxicity. In addition, promising novel proteasome inhibitors, which are distinct from bortezomib, and exhibit equipotent anti-multiple myeloma activities, are undergoing clinical evaluation in order to improve patient outcome in multiple myeloma. Republished from Current BioData's Targeted Proteins database (TPdb; ).
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spelling pubmed-25828022008-11-14 Targeting the UPS as therapy in multiple myeloma Chauhan, Dharminder Bianchi, Giada Anderson, Kenneth C BMC Biochem Review The coordinated regulation of cellular protein synthesis and degradation is essential for normal cellular functioning. The ubiquitin proteasome system mediates the intracellular protein degradation that is required for normal cellular homeostasis. The 26S proteasome is a multi-enzyme protease that degrades redundant proteins; conversely, inhibition of proteasomal degradation results in intracellular aggregation of unwanted proteins and cell death. This observation led to the development of proteasome inhibitors as therapeutics for use in cancer. The clinical applicability of targeting proteasomes is exemplified by the recent FDA approval of the first proteasome inhibitor, bortezomib, for the treatment of relapsed/refractory multiple myeloma. Although bortezomib represents a major advance in the treatment of this disease, it can be associated with toxicity and the development of drug resistance. Importantly, extensive preclinical studies suggest that combination therapies can both circumvent drug resistance and reduce toxicity. In addition, promising novel proteasome inhibitors, which are distinct from bortezomib, and exhibit equipotent anti-multiple myeloma activities, are undergoing clinical evaluation in order to improve patient outcome in multiple myeloma. Republished from Current BioData's Targeted Proteins database (TPdb; ). BioMed Central 2008-10-21 /pmc/articles/PMC2582802/ /pubmed/19007431 http://dx.doi.org/10.1186/1471-2091-9-S1-S1 Text en Copyright © 2008 Chauhan et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Chauhan, Dharminder
Bianchi, Giada
Anderson, Kenneth C
Targeting the UPS as therapy in multiple myeloma
title Targeting the UPS as therapy in multiple myeloma
title_full Targeting the UPS as therapy in multiple myeloma
title_fullStr Targeting the UPS as therapy in multiple myeloma
title_full_unstemmed Targeting the UPS as therapy in multiple myeloma
title_short Targeting the UPS as therapy in multiple myeloma
title_sort targeting the ups as therapy in multiple myeloma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582802/
https://www.ncbi.nlm.nih.gov/pubmed/19007431
http://dx.doi.org/10.1186/1471-2091-9-S1-S1
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