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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Bortezomib as an Antitumor Agent

Author(s): A. M. Roccaro, T. Hideshima, P. G. Richardson, D. Russo, D. Ribatti, A. Vacca, F. Dammacco and K. C. Anderson

Volume 7, Issue 6, 2006

Page: [441 - 448] Pages: 8

DOI: 10.2174/138920106779116865

Price: $65

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)


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