Abstract
The intracellular concentration of proteins in both normal and tumor cells are regulated by the balance between the rates of protein synthesis vs. degradation. The ubiquitin-proteasome pathway is the main intracellular cascade for controlled degradation of proteins and has attracted in recent years major interest not only because of its biochemical complexity and the intricate regulation of its function, but also because diverse cell cycle regulators and modulators of apoptosis are subject to regulation by proteasome function, and can therefore be significantly affected by small molecule inhibitors of the proteolytic activity of the proteasome. In fact, bortezomib, the prototypic member of this class of agents, was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma patients. This review article focuses on the exciting recent progress in the use of proteasome inhibitors, with emphasis on the bench-to-bedside research effort which provided the foundation for clinical development of bortezomib for the treatment of multiple myeloma, as well as other hematologic malignancies, such as mantle cell lymphoma.
Keywords: Proteasome, PS-341, bortezomib, multiple myeloma, apoptosis, combination therapies
Current Drug Targets
Title: Proteasome Inhibition as a New Therapeutic Principle in Hematological Malignancies
Volume: 7 Issue: 10
Author(s): Constantine S. Mitsiades, Nicholas Mitsiades, Teru Hideshima, Paul G. Richardson and Kenneth C. Anderson
Affiliation:
Keywords: Proteasome, PS-341, bortezomib, multiple myeloma, apoptosis, combination therapies
Abstract: The intracellular concentration of proteins in both normal and tumor cells are regulated by the balance between the rates of protein synthesis vs. degradation. The ubiquitin-proteasome pathway is the main intracellular cascade for controlled degradation of proteins and has attracted in recent years major interest not only because of its biochemical complexity and the intricate regulation of its function, but also because diverse cell cycle regulators and modulators of apoptosis are subject to regulation by proteasome function, and can therefore be significantly affected by small molecule inhibitors of the proteolytic activity of the proteasome. In fact, bortezomib, the prototypic member of this class of agents, was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma patients. This review article focuses on the exciting recent progress in the use of proteasome inhibitors, with emphasis on the bench-to-bedside research effort which provided the foundation for clinical development of bortezomib for the treatment of multiple myeloma, as well as other hematologic malignancies, such as mantle cell lymphoma.
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Mitsiades S. Constantine, Mitsiades Nicholas, Hideshima Teru, Richardson G. Paul and Anderson C. Kenneth, Proteasome Inhibition as a New Therapeutic Principle in Hematological Malignancies, Current Drug Targets 2006; 7 (10) . https://dx.doi.org/10.2174/138945006778559247
DOI https://dx.doi.org/10.2174/138945006778559247 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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