Document Detail


The immunoproteasome as a target in hematologic malignancies.
MedLine Citation:
PMID:  22726549     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Suppression of proteasome function with the first-in-class small molecule inhibitor bortezomib is a rational therapeutic strategy against several hematologic malignancies, including multiple myeloma and mantle cell lymphoma. Second-generation inhibitors such as carfilzomib, ixazomib, and marizomib that, like bortezomib, target both the constitutive proteasome and the immunoproteasome, are also in clinical trials and showing encouraging activity. While the efficacy of these agents is well documented, toxicities associated with their use, such as peripheral neuropathy and gastrointestinal effects, can necessitate dose reductions or even discontinuations, possibly hampering their anti-neoplastic effects. These findings suggested that it could be possible to improve the therapeutic index of this class of drugs by specifically targeting only the immunoproteasome. Since the immunoproteasome is a unique target found in lymphoid-derived cells, immunoproteasome-specific inhibitors (IPSIs) could preserve efficacy while reducing treatment-emergent toxicities since they would spare other tissues with little to no immunoproteasome expression. This review discusses the current state of development of IPSIs, and the potential of using such agents for the treatment of hematologic malignancies.
Authors:
Deborah J Kuhn; Robert Z Orlowski
Related Documents :
17939299 - Bone marrow niche and leukemia.
22283809 - Development of novel cxcr4-based therapeutics.
17670939 - Stable reduction of ccr5 by rnai through hematopoietic stem cell transplant in non-huma...
3356309 - Mice exposed in utero to 20 ppm benzene exhibit altered numbers of recognizable hematop...
9502719 - A xenopus homologue of aml-1 reveals unexpected patterning mechanisms leading to the fo...
17374609 - The cxcl12, periostin, and ccl9 genes are direct targets for early b-cell factor in op-...
8830829 - Interleukin-1 alpha-mediated promotion of long-term alloengraftment and short-term neut...
15261829 - Lhx2 is expressed in the septum transversum mesenchyme that becomes an integral part of...
18442329 - Have we reached the point for in vivo rejuvenation?
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Seminars in hematology     Volume:  49     ISSN:  1532-8686     ISO Abbreviation:  Semin. Hematol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-25     Completed Date:  2013-06-10     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0404514     Medline TA:  Semin Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  258-62     Citation Subset:  IM    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*,  therapeutic use
Hematologic Neoplasms / drug therapy*,  enzymology*,  immunology,  pathology
Humans
Proteasome Endopeptidase Complex / immunology*,  metabolism*
Proteasome Inhibitors / pharmacology*,  therapeutic use
Grant Support
ID/Acronym/Agency:
1K99 CA149140/CA/NCI NIH HHS; K99 CA149140/CA/NCI NIH HHS; P50 CA142509/CA/NCI NIH HHS; P50 CA142509/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Proteasome Inhibitors; EC 3.4.25.1/Proteasome Endopeptidase Complex
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  General aspects and mechanisms of peripheral neuropathy associated with bortezomib in patients with ...
Next Document:  Proteasome inhibition for antibody-mediated allograft rejection.