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
-
Tankyrase Inhibitors as Therapeutic Targets for Cancer
Current Topics in Medicinal Chemistry Lupus Nephritis: A Treatment Update
Current Clinical Pharmacology Protein Interaction Networks in Metallo Proteins and Docking Approaches of Metallic Compounds with TIMP and MMP in Control of MAPK Pathway
Letters in Drug Design & Discovery Osteoporotic Fracture Healing: Potential Use of Medicinal Plants from the Tropics
Current Drug Targets Novel Glitazones with Diverse Peroxisome Proliferator Activated Receptor Modulatory Potential
Current Bioactive Compounds New Robotic Technologies in Cancer Colon Screening
Clinical Cancer Drugs Targeting Pain-evoking Transient Receptor Potential Channels for the Treatment of Pain
Current Neuropharmacology Anticancer Potential of Dietary Natural Products: A Comprehensive Review
Anti-Cancer Agents in Medicinal Chemistry Transductional Targeting with Recombinant Adenovirus Vectors
Current Gene Therapy Molecular and Cellular Mechanisms of Hexavalent Chromium-Induced Lung Cancer: An Updated Perspective
Current Drug Metabolism Analysis of the Salivary Microbiome in the Periodontal Disease Patients with Hypertension and Non-hypertension
Current Bioinformatics Obesity in China: What are the Causes?
Current Pharmaceutical Design Physical and Chemical Stimuli-Responsive Drug Delivery Systems: Targeted Delivery and Main Routes of Administration
Current Pharmaceutical Design Puerarin: A Review on the Pharmacological Activity, Chemical Properties and Pharmacokinetics of Main Isoflavonoid
The Natural Products Journal Experimental Onco-Immunology Revisited
Current Cancer Therapy Reviews Postoperative Radiotherapy After Radical Prostatectomy: Adjuvant or Salvage?
Current Cancer Therapy Reviews Renal and Hepatic Kinetics of Tc-99m-labelled Hexakis-methoxy-isobutyl Isonitrile
Drug Metabolism Letters Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology Medicinal Plants for the Prevention and Treatment of Bacterial Infections
Current Pharmaceutical Design Downstream Carcinogenesis Signaling Pathways by Green Tea Polyphenols: A Translational Perspective of Chemoprevention and Treatment for Cancers
Current Drug Metabolism