Proteasome inhibition as a new therapeutic principle in hematological malignancies.

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.

• Authors: Constantine S Mitsiades, Nicholas Mitsiades, Teru Hideshima, Paul G Richardson, Kenneth C Anderson
• Journal: Current drug targets (Curr Drug Targets) Vol. 7 Issue 10 Pg. 1341-7 (Oct 2006) ISSN: 1873-5592 [Electronic] United Arab Emirates
• PMID: 17073596 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Protease Inhibitors
• Proteasome Inhibitors
• Proteasome Endopeptidase Complex

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Hematologic Neoplasms (blood, drug therapy, enzymology)
• Humans
• Protease Inhibitors (pharmacology, therapeutic use)
• Proteasome Endopeptidase Complex (blood)
• Proteasome Inhibitors