| The immunoproteasome as a target in hematologic malignancies. | |
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MedLine Citation:
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PMID: 22726549 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Deborah J Kuhn; Robert Z Orlowski |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Seminars in hematology Volume: 49 ISSN: 1532-8686 ISO Abbreviation: Semin. Hematol. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0404514 Medline TA: Semin Hematol Country: United States |
Other Details:
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Languages: eng Pagination: 258-62 Citation Subset: IM |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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