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The immunoproteasome as a therapeutic target for hematological malignancies.

Authors
  • Miller, Zachary
  • Lee, Wooin
  • Kim, Kyung Bo
Type
Published Article
Journal
Current Cancer Drug Targets
Publisher
Bentham Science
Publication Date
Jan 01, 2014
Volume
14
Issue
6
Pages
537–548
Identifiers
PMID: 25059201
Source
Medline
License
Unknown

Abstract

Remarkable successes with the FDA-approved proteasome inhibitors bortezomib (Velcade(®)) and carfilzomib (Kyprolis(®)) have proved that the proteasome is an effective target for the treatment of multiple myeloma. In other hematological malignancies, however, clinical trials of proteasome-targeting drugs have shown generally disappointing results to date. Additionally, existing proteasome inhibitors have significant issues with toxicity, poor response rate, and the emergence of resistance for many patients. A new generation of small-molecule therapies specifically targeting the immunoproteasome may have the potential to overcome the drawbacks of bortezomib and carfilzomib in multiple myeloma and to bring significant benefits of proteasome inhibitor therapies to many more patients. In this article, we describe the potential of the immunoproteasome as a therapeutic target for hematological malignancies and the recent progress in the development of useful immunoproteasome inhibitors.

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