Targeting the proteasome in mantle cell lymphoma: a promising therapeutic approach.

Abstract

Mantle cell lymphoma (MCL) is a distinctive non-Hodgkin's lymphoma sub-type, characterized by over-expression of cyclin D1 as a consequence of chromosomal translocation t(11;14)(q13;q32). MCL remains an incurable disease, combining the unfavorable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL, which is often associated with additional cytogenetic alterations, has an even worse prognosis and new treatment options are clearly needed. The 26S proteasome is a large multi-catalytic multi-protein complex, present in all eukaryotic cells. It is responsible for the degradation of a variety of short-lived proteins and exhibits a key position in cellular processes including apoptosis and cell cycle progression. Targeting the ubiquitin - proteasome pathway has only recently been identified as a promising new therapeutic option for cancer patients. Interestingly, an increased activity of the proteasome pathway has been described in MCL cells and the inhibition of the proteasome seems to be a promising therapeutic approach for this incurable disease.

• Authors: Christian Bogner, Christian Peschel, Thomas Decker
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 47 Issue 2 Pg. 195-205 (Feb 2006) ISSN: 1042-8194 [Print] United States
• PMID: 16321849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Boronic Acids
• Protease Inhibitors
• Proteasome Inhibitors
• Pyrazines
• Ubiquitin
• Bortezomib
• Proteasome Endopeptidase Complex

Topics

• Boronic Acids (pharmacology, therapeutic use)
• Bortezomib
• Humans
• Lymphoma, Mantle-Cell (diagnosis, drug therapy, metabolism)
• Protease Inhibitors (therapeutic use)
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors
• Pyrazines (pharmacology, therapeutic use)
• Structure-Activity Relationship
• Ubiquitin (metabolism)