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.
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Thyroid Ultrasound and Other Imaging Procedures in the Pediatric Age
Current Pediatric Reviews Cdc20: A Potential Novel Therapeutic Target for Cancer Treatment
Current Pharmaceutical Design Cruciferous Plants: Phytochemical Toxicity Versus Cancer Chemoprotection
Mini-Reviews in Medicinal Chemistry Natural Products as Anticancer Agents
Current Drug Targets Bcl-2 Proteins: Targets and Tools for Chemosensitisation of Tumor Cells
Current Medicinal Chemistry - Anti-Cancer Agents Occurrence and Severity of Adverse Reactions of Immune Checkpoint Inhibitors (PD-1 and PD L1) Based on Mordovian Dispensary Data Analysis
Current Cancer Therapy Reviews Editorial (Thematic Issue: Immunophilins, Protein Chemistry and Cell Biology of a Promising New Class of Drug Targets – Part II)
Current Molecular Pharmacology Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice
Current Gene Therapy Recent Advances in the Synthesis of 1,3-Azoles
Current Topics in Medicinal Chemistry Cathepsin D as a Promising Target for the Discovery of Novel Anticancer Agents
Current Cancer Drug Targets Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting
Current Molecular Pharmacology Oxidative Stress and Cancer: The Role of Nrf2
Current Cancer Drug Targets PI3K Pathway Inhibitors: Better Not Left Alone
Current Pharmaceutical Design Modulation of Porcine (Sus scrofa domestica) and Pheasant (Phasianus colchicus) Carbonyl Reducing Enzymes by Anthelmintic Therapy with Flubendazole
Drug Metabolism Letters Combined Treatment with CCI779 and SB203580 Induces Cellular Senescence in Renal Cell Carcinoma Cell Line via p53 Pathway
Anti-Cancer Agents in Medicinal Chemistry Drugging Cell Cycle Kinases in Cancer Therapy
Current Drug Targets Functions of S100 Proteins
Current Molecular Medicine Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions
Current Medicinal Chemistry The Relevance of IgE in the Pathogenesis of Allergy: The Effect of an Anti-IgE Drug in Asthma and Other Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Fiber Optic Sensors for Biomedical Applications
Current Analytical Chemistry