Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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The Immunoproteasome as a Therapeutic Target for Hematological Malignancies

Author(s): Zachary Miller, Wooin Lee and Kyung Bo Kim

Affiliation: Department of Pharmaceutical Sciences, University of Kentucky, 789 South Limestone, Lexington, KY 40536, USA.

Keywords: Constitutive proteasome, immunoproteasome, mantle cell lymphoma, multiple myeloma, small molecule inhibitors, subunit-selective inhibitor.

Graphical Abstract:


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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Article Details

VOLUME: 14
ISSUE: 6
Page: [537 - 548]
Pages: 12
DOI: 10.2174/1568009614666140723113139