Abstract
The intracellular concentration of proteins in both normal and tumor cells are regulated by the balance between the rates of protein synthesis vs. degradation. The ubiquitin-proteasome pathway is the main intracellular cascade for controlled degradation of proteins and has attracted in recent years major interest not only because of its biochemical complexity and the intricate regulation of its function, but also because diverse cell cycle regulators and modulators of apoptosis are subject to regulation by proteasome function, and can therefore be significantly affected by small molecule inhibitors of the proteolytic activity of the proteasome. In fact, bortezomib, the prototypic member of this class of agents, was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma patients. This review article focuses on the exciting recent progress in the use of proteasome inhibitors, with emphasis on the bench-to-bedside research effort which provided the foundation for clinical development of bortezomib for the treatment of multiple myeloma, as well as other hematologic malignancies, such as mantle cell lymphoma.
Keywords: Proteasome, PS-341, bortezomib, multiple myeloma, apoptosis, combination therapies
Current Drug Targets
Title: Proteasome Inhibition as a New Therapeutic Principle in Hematological Malignancies
Volume: 7 Issue: 10
Author(s): Constantine S. Mitsiades, Nicholas Mitsiades, Teru Hideshima, Paul G. Richardson and Kenneth C. Anderson
Affiliation:
Keywords: Proteasome, PS-341, bortezomib, multiple myeloma, apoptosis, combination therapies
Abstract: The intracellular concentration of proteins in both normal and tumor cells are regulated by the balance between the rates of protein synthesis vs. degradation. The ubiquitin-proteasome pathway is the main intracellular cascade for controlled degradation of proteins and has attracted in recent years major interest not only because of its biochemical complexity and the intricate regulation of its function, but also because diverse cell cycle regulators and modulators of apoptosis are subject to regulation by proteasome function, and can therefore be significantly affected by small molecule inhibitors of the proteolytic activity of the proteasome. In fact, bortezomib, the prototypic member of this class of agents, was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma patients. This review article focuses on the exciting recent progress in the use of proteasome inhibitors, with emphasis on the bench-to-bedside research effort which provided the foundation for clinical development of bortezomib for the treatment of multiple myeloma, as well as other hematologic malignancies, such as mantle cell lymphoma.
Export Options
About this article
Cite this article as:
Mitsiades S. Constantine, Mitsiades Nicholas, Hideshima Teru, Richardson G. Paul and Anderson C. Kenneth, Proteasome Inhibition as a New Therapeutic Principle in Hematological Malignancies, Current Drug Targets 2006; 7 (10) . https://dx.doi.org/10.2174/138945006778559247
DOI https://dx.doi.org/10.2174/138945006778559247 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...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
-
Regulation and Importance of the PI3K/Akt/mTOR Signaling Pathway in Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Development of Vascular Endothelial Growth Factor Receptor (VEGFR) Kinase Inhibitors as Anti-Angiogenic Agents in Cancer Therapy
Current Medicinal Chemistry Tyrosine Kinase Inhibitors – A Review on Pharmacology, Metabolism and Side Effects
Current Drug Metabolism Chronic Eosinophilic Leukemia, Not Otherwise Specified (CEL, NOS)
Current Cancer Therapy Reviews Nucleic Acids as Therapeutic Agents
Current Topics in Medicinal Chemistry The Genetic and Epigenetic Effects of 5-Azacytidine and its Major Breakdown Product Guanylurea
Epigenetic Diagnosis & Therapy (Discontinued) FLT3 as a Therapeutic Target in Childhood Acute Leukemia
Current Drug Targets Targeting the EGFR Pathway for Cancer Therapy
Current Medicinal Chemistry Cytostatic Effect of the Nucleoside Analogue 2-Chloroadenosine on Human Prostate Cancer Cell Line
Current Pharmaceutical Analysis Pain Management in Hematological Patients with Major Organ Dysfunctions and Comorbid Illnesses
Cardiovascular & Hematological Agents in Medicinal Chemistry Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Chemistry and Pharmacology of Angiotensin-Converting Enzyme Inhibitors
Current Pharmaceutical Design Anti-VEGF Strategies – from Antibodies to Tyrosine Kinase Inhibitors: Background and Clinical Development in Human Cancer
Current Pharmaceutical Design Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates
Current Topics in Medicinal Chemistry CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery
Current Drug Targets Statins and Type 2 Diabetes Mellitus: An Update After 1 Year
Current Pharmaceutical Design Targeting MDM2 and MDMX in Retinoblastoma
Current Cancer Drug Targets Heat Shock Protein 90 Inhibitors as Therapeutic Agents
Recent Patents on Anti-Cancer Drug Discovery Current Status of Epigenetics and Anticancer Drug Discovery
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot Topic: Targeted Therapies in Oncology (Guest Editor: Monica M. Mita)]
Current Drug Targets