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 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- 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
-
Recombinant Snake Venom Cystatin Inhibits Tumor Angiogenesis in vitro and in vivo Associated with Downregulation of VEGF-A165, Flt-1 and bFGF
Anti-Cancer Agents in Medicinal Chemistry Should we Target Allergen Protease Activity to Decrease the Burden of Allergic Airway Inflammation?
Inflammation & Allergy - Drug Targets (Discontinued) The Role of Snail in EMT and Tumorigenesis
Current Cancer Drug Targets Radiolabeled Imaging Probes Targeting Angiogenesis for Personalized Medicine
Current Pharmaceutical Design Proteomics in Computer-Aided Drug Design
Current Computer-Aided Drug Design Cancer Risk and Nullity of Glutathione-S-Transferase Mu and Theta 1 in Occupational Pesticide Workers
Current Pharmaceutical Biotechnology Simplified Receptor Based Pharmacophore Approach to Retrieve Potent PTP-LAR Inhibitors Using Apoenzyme
Current Computer-Aided Drug Design Mining Sarcomas by Proteomics Approaches: Ewing Sarcoma on the Spotlight
Recent Patents on Biotechnology Microtubule Targeting Agents: A Benchmark in Cancer Therapy
Current Drug Therapy Potentials of Hydrogels in Cancer Therapy
Current Cancer Therapy Reviews Aberrant Splicing, Hyaluronan Synthases and Intracellular Hyaluronan as Drivers of Oncogenesis and Potential Drug Targets
Current Cancer Drug Targets Patent Selections
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Radiosensitization of Prostate Cancer by Soy Isoflavones
Current Cancer Drug Targets Insulin Resistance the Link between T2DM and CVD: Basic Mechanisms and Clinical Implications
Current Vascular Pharmacology Inhibition of Procarcinogen Activating Enzyme CYP1A2 Activity and Free Radical Formation by Caffeic Acid and its Amide Analogues
Drug Metabolism Letters The Apoptosis Mechanism of Epirubicin Combined with BCG on Human Bladder Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Diabetes and Nutritional Screening in Post-Bariatric Patients
Current Diabetes Reviews Phytotherapeutic Agents for Benign Prostatic Hyperplasia: An Overview
Mini-Reviews in Medicinal Chemistry Polymeric Carriers for Gene Delivery: Chitosan and Poly(amidoamine) Dendrimers
Current Pharmaceutical Design The Thyroid Gland: A Crossroad in Inflammation-Induced Carcinoma? An Ongoing Debate with New Therapeutic Potential.
Current Medicinal Chemistry