Abstract
Tetrathiomolybdate (TM) is a novel anticopper agent under development for use in Wilsons disease. It acts by forming a stable tripartite complex with serum albumin and copper, rendering the complexed copper unavailable for cellular uptake. TM is a very potent anticopper agent and has an excellent safety profile. It has been shown that normal copper levels are required for optimal angiogenesis. Based on this background, we decided to evaluate TM as an anticancer agent. TM treatment of Her/2neu mice, genetically programmed to develop breast cancer, completely prevented the development of visible mammary cancers, although avascular microscopic clusters of cancer cells were present in the breasts of TM treated animals. Controls developed grossly visible tumors. TM was able to strongly inhibit tumor growth in six other rodent models. In a phase 1/2 clinical trial of advanced and metastatic cancers, freedom from progression averaged 11 months, and some individual results were quite dramatic. Eight phase 2 studies of specific cancers have been launched. TMs hypothesized mechanism of action is inhibition of angiogenic cytokines. Unlike other current approaches to antiangiogenic therapy which target single agents, we hypothesize that TM inhibits multiple angiogenic cytokines. Part of this effect appears to stem from inhibition of nuclear factor kappa B (NFKB), which in turn controls transcription of many angiogenic and other cytokines. However, there are probably multiple mechanisms, in that some angiogenic cytokines appear to have separate mechanisms of copper dependence. The inhibition of multiple angiogenic cytokines gives TM the potential to be a more global inhibitor of angiogenesis.
Keywords: tetrathiomolybdate, copper, cancer, angiogenesis, vascular endothelial growth factor, copper deficiency, wilsons disease
Current Cancer Drug Targets
Title: Copper Lowering Therapy With Tetrathiomolybdate as an Antiangiogenic Strategy in Cancer
Volume: 5 Issue: 3
Author(s): George J. Brewer
Affiliation:
Keywords: tetrathiomolybdate, copper, cancer, angiogenesis, vascular endothelial growth factor, copper deficiency, wilsons disease
Abstract: Tetrathiomolybdate (TM) is a novel anticopper agent under development for use in Wilsons disease. It acts by forming a stable tripartite complex with serum albumin and copper, rendering the complexed copper unavailable for cellular uptake. TM is a very potent anticopper agent and has an excellent safety profile. It has been shown that normal copper levels are required for optimal angiogenesis. Based on this background, we decided to evaluate TM as an anticancer agent. TM treatment of Her/2neu mice, genetically programmed to develop breast cancer, completely prevented the development of visible mammary cancers, although avascular microscopic clusters of cancer cells were present in the breasts of TM treated animals. Controls developed grossly visible tumors. TM was able to strongly inhibit tumor growth in six other rodent models. In a phase 1/2 clinical trial of advanced and metastatic cancers, freedom from progression averaged 11 months, and some individual results were quite dramatic. Eight phase 2 studies of specific cancers have been launched. TMs hypothesized mechanism of action is inhibition of angiogenic cytokines. Unlike other current approaches to antiangiogenic therapy which target single agents, we hypothesize that TM inhibits multiple angiogenic cytokines. Part of this effect appears to stem from inhibition of nuclear factor kappa B (NFKB), which in turn controls transcription of many angiogenic and other cytokines. However, there are probably multiple mechanisms, in that some angiogenic cytokines appear to have separate mechanisms of copper dependence. The inhibition of multiple angiogenic cytokines gives TM the potential to be a more global inhibitor of angiogenesis.
Export Options
About this article
Cite this article as:
Brewer J. George, Copper Lowering Therapy With Tetrathiomolybdate as an Antiangiogenic Strategy in Cancer, Current Cancer Drug Targets 2005; 5 (3) . https://dx.doi.org/10.2174/1568009053765807
DOI https://dx.doi.org/10.2174/1568009053765807 |
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
-
Azo Reductase- Activated Colon- Targeting Prodrugs of Aminosalicylates for Inflammatory Bowel Disease: Preparation, Pharmacokinetic and Pharmacodynamic Profile
Inflammation & Allergy - Drug Targets (Discontinued) Ryanodine Receptors for Drugs and Insecticides: An Overview
Mini-Reviews in Medicinal Chemistry Emerging Role of Stromal Fibroblasts in Epithelial Cancer
Current Signal Transduction Therapy Nanocrystals: From Raw Material to the Final Formulated Oral Dosage Form - A Review
Current Pharmaceutical Design Food and Food Supplements with Hypocholesterolemic Effects
Recent Patents on Food, Nutrition & Agriculture Does More MnSOD Mean More Hydrogen Peroxide?
Anti-Cancer Agents in Medicinal Chemistry CETUXIMAB: From Bench to Bedside
Current Cancer Drug Targets Emerging Use of Nanotechnology in the Treatment of Neurological Disorders
Current Pharmaceutical Design Molecule of the Month
Current Topics in Medicinal Chemistry Preparation, Characterization and <i>In Vitro</i> Biological Evaluation of Novel Curcumin Derivatives as Cytotoxic and Apoptosis-Inducing Agents
Anti-Cancer Agents in Medicinal Chemistry Epigenetic Modulation Using Small Molecules - Targeting Histone Acetyltransferases in Disease
Current Medicinal Chemistry Implications of Melatonin Therapy in Irritable Bowel Syndrome: A Systematic Review
Current Pharmaceutical Design Pharmaceutical Measures to Prevent Doxorubicin-Induced Cardiotoxicity
Mini-Reviews in Medicinal Chemistry Is Senescence Reversible?
Current Drug Targets αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology
Current Topics in Medicinal Chemistry Application of Nanotechnology in the Treatment and Diagnosis of Gastrointestinal Cancers: Review of Recent Patents
Recent Patents on Anti-Cancer Drug Discovery P53 Gene Therapy Sensitizes Resistant Breast Cancer Cells to Doxorubicin Chemotherapy
Drug Delivery Letters Recent Patents on Anti-Cancer Potential of Helenalin
Recent Patents on Anti-Cancer Drug Discovery Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets Modulation of Apoptosis: New Opportunities for Drug Discovery to Treat Autoimmune Thyroiditis
Recent Patents on Inflammation & Allergy Drug Discovery