Abstract
The ubiquitin-proteasome pathway (UPP) is the major non-lysosomal proteolytic system in the cytosol and nucleus of all eukaryotic cells. Bortezomib (also known as PS-341 and Velcade™) is a proteasome inhibitor, a novel class of cancer therapies. Bortezomib blocks multi-ubiquitinated protein degradation by inhibiting 26S proteasome activity, including regulating cell cycle, anti-apoptosis, and inflammation, as well as immune surveillance. In multiple myeloma (MM) cells, bortezomib directly induces cell stress response followed by activation of c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK), and triggers caspase-dependent apoptosis of tumor cells. Recent clinical studies demonstrated that bortezomib had remarkable anti-tumor activity in refractory and relapsed MM, providing the basis to approval by FDA. Its anti-tumor activities earlier in the course, in combination therapies, and in other malignancies is ongoing.
Keywords: Apoptosis, Cell Adhesion, Cytokine, Proteasome inhibitors, Anti-Angiogenesis, Multiple Myeloma (MM)
Current Pharmaceutical Biotechnology
Title: Bortezomib as an Antitumor Agent
Volume: 7 Issue: 6
Author(s): A. M. Roccaro, T. Hideshima, P. G. Richardson, D. Russo, D. Ribatti, A. Vacca, F. Dammacco and K. C. Anderson
Affiliation:
Keywords: Apoptosis, Cell Adhesion, Cytokine, Proteasome inhibitors, Anti-Angiogenesis, Multiple Myeloma (MM)
Abstract: The ubiquitin-proteasome pathway (UPP) is the major non-lysosomal proteolytic system in the cytosol and nucleus of all eukaryotic cells. Bortezomib (also known as PS-341 and Velcade™) is a proteasome inhibitor, a novel class of cancer therapies. Bortezomib blocks multi-ubiquitinated protein degradation by inhibiting 26S proteasome activity, including regulating cell cycle, anti-apoptosis, and inflammation, as well as immune surveillance. In multiple myeloma (MM) cells, bortezomib directly induces cell stress response followed by activation of c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK), and triggers caspase-dependent apoptosis of tumor cells. Recent clinical studies demonstrated that bortezomib had remarkable anti-tumor activity in refractory and relapsed MM, providing the basis to approval by FDA. Its anti-tumor activities earlier in the course, in combination therapies, and in other malignancies is ongoing.
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Roccaro M. A., Hideshima T., Richardson G. P., Russo D., Ribatti D., Vacca A., Dammacco F. and Anderson C. K., Bortezomib as an Antitumor Agent, Current Pharmaceutical Biotechnology 2006; 7 (6) . https://dx.doi.org/10.2174/138920106779116865
DOI https://dx.doi.org/10.2174/138920106779116865 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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