Abstract
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IκB breakdown and the related stabilization of NFκB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved in patients treated with bortezomib and dexamethasone compared to dexamethasone alone. These results have induced several researchers to suggest preclinical and clinical studies for the application of bortezomib in solid tumors. Preclinical data have proved useful in the identification of several of the biological processes implicated, including cell cycle arrest at the G2/M phase, upregulation of p21, apoptosis regulation, microvessel density reduction, overcoming chemotherapy resistance. The clinical results obtained so far with the use of bortezomib in patients with solid malignancies are still not sufficient for the introduction of the drug into clinical practice. Furthermore, the results obtained with the use of bortezomib combined with cytotoxic drugs have not proved any more satisfactory than those obtained with bortezomib used as a single agent. Other preclinical studies are required in order to reach a clearer understanding of the relevance of bortezomib in the therapy of solid tumors.
Keywords: Bortezomib, solid tumors, proteasome inhibition
Current Cancer Drug Targets
Title: Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment
Volume: 10 Issue: 1
Author(s): A. Russo, G. Bronte, F. Fulfaro, G. Cicero, V. Adamo, N. Gebbia and S. Rizzo
Affiliation:
Keywords: Bortezomib, solid tumors, proteasome inhibition
Abstract: Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IκB breakdown and the related stabilization of NFκB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved in patients treated with bortezomib and dexamethasone compared to dexamethasone alone. These results have induced several researchers to suggest preclinical and clinical studies for the application of bortezomib in solid tumors. Preclinical data have proved useful in the identification of several of the biological processes implicated, including cell cycle arrest at the G2/M phase, upregulation of p21, apoptosis regulation, microvessel density reduction, overcoming chemotherapy resistance. The clinical results obtained so far with the use of bortezomib in patients with solid malignancies are still not sufficient for the introduction of the drug into clinical practice. Furthermore, the results obtained with the use of bortezomib combined with cytotoxic drugs have not proved any more satisfactory than those obtained with bortezomib used as a single agent. Other preclinical studies are required in order to reach a clearer understanding of the relevance of bortezomib in the therapy of solid tumors.
Export Options
About this article
Cite this article as:
Russo A., Bronte G., Fulfaro F., Cicero G., Adamo V., Gebbia N. and Rizzo S., Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment, Current Cancer Drug Targets 2010; 10 (1) . https://dx.doi.org/10.2174/156800910790980250
DOI https://dx.doi.org/10.2174/156800910790980250 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Inhalation Gases or Gaseous Mediators As Neuroprotectants for Cerebral Ischaemia
Current Drug Targets Early Cerebral Infarction Following Aneurysmal Subarachnoid Hemorrhage: Frequency, Risk Factors, Patterns, and Prognosis
Current Neurovascular Research Data-driven Approach to Detect and Predict Adverse Drug Reactions
Current Pharmaceutical Design The Role of Protease-Activated Receptors for the Development of Myocarditis: Possible Therapeutic Implications
Current Pharmaceutical Design Members of CRF Family and their Receptors: From Past to Future
Current Medicinal Chemistry Putative Role for Apelin in Pressure/Volume Homeostasis and Cardiovascular Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Heart Failure in South America
Current Cardiology Reviews Oxidative Stress and Mitochondrial Dysfunction in Sepsis: A Potential Therapy with Mitochondria-Targeted Antioxidants
Infectious Disorders - Drug Targets Vasopressin and Oxytocin in Control of the Cardiovascular System
Current Neuropharmacology Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Current Stem Cell Research & Therapy Beta-Blockers use for Hypertension in the Elderly
Cardiovascular & Hematological Agents in Medicinal Chemistry Machine Learning Approaches in Parkinson’s Disease
Current Medicinal Chemistry Pharmacokinetics of Topical Ocular Drug Delivery: Potential Uses for the Treatment of Diseases of the Posterior Segment and Beyond
Current Drug Metabolism Recent Progress in the Development of Adenosine Receptor Ligands as Antiinflammatory Drugs
Current Topics in Medicinal Chemistry Calcium Related Genes in Dogs as Potential Cardiac Biomarkers for the Detection of Chronic Mitral Valve Disease
Recent Patents on Biomarkers Current Biological Therapies for Inflammatory Bowel Disease
Current Pharmaceutical Design The Molecular Basis of Class Side Effects Due to Treatment with Inhibitors of the VEGF/VEGFR Pathway
Current Clinical Pharmacology Carotid Baroreceptor Stimulation: A Promising Approach for the Management of Resistant Hypertension and Heart Failure
Current Vascular Pharmacology Dopexamine After Heart Surgery: An Uncommonly Used, Though Useful Inotropic Agent
Recent Patents on Cardiovascular Drug Discovery Carnitine Metabolism and Deficit - When Supplementation is Necessary?
Current Pharmaceutical Biotechnology