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
-
Recent Advances in Gene Therapy of Endometriosis
Recent Patents on DNA & Gene Sequences Growth Factors, Cytokines and Dendritic Cell Development
Current Pharmaceutical Design Cytotoxicity and Anti-Inflammatory Effects of Polyherbal Formulations, Joint Pain Spl and Rumalaya Forte on Lipopolysaccharide Induced Inflammation in IC-21 Macrophages
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Prodigiosins as Anti Cancer Agents: Living Upto Their Name
Current Pharmaceutical Design Recent Advance in Drug Development of Squamous Cell Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic Communication, and Pharmacological Relevance
Current Medicinal Chemistry Design, Optimization and Characterization of Nanostructured Lipid Carriers of Raloxifene Hydrochloride for Transdermal Delivery
Nanoscience & Nanotechnology-Asia Glucose Blood Levels as a Therapeutic Target in Acute Ischaemic Stroke Setting
Current Topics in Medicinal Chemistry Computational Protein Design: A Novel Path to Future Protein Drugs
Current Pharmaceutical Design The Role of Pemetrexed in Lung Adenocarcinoma, Mixed Subtype with Bronchioloalveolar Carcinoma Features
Current Drug Targets Synthesis, In Vitro Anticancer, Anti-Inflammatory and DNA Binding Activity of Thiazolidinedione Derivatives
Anti-Cancer Agents in Medicinal Chemistry Distinctive Cellular Roles for Novel Protein Kinase C Isoenzymes
Current Pharmaceutical Design The Function of the Selective Inhibitors of Cycloxygenase 2
Mini-Reviews in Medicinal Chemistry Nutritional Modulation of Terminal End Buds: Its Relevance to Breast Cancer Prevention
Current Cancer Drug Targets Novel Carriers for Controlled Site Specific Delivery of Anti-Inflammatory Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Experimental Breast Cancer Models: Preclinical Imaging Perspective
Current Radiopharmaceuticals Radioligands for the Angiotensin II Subtype 1 (AT1) Receptor
Current Topics in Medicinal Chemistry Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy
CNS & Neurological Disorders - Drug Targets From ImmunoToxins to ImmunoRNases
Current Pharmaceutical Biotechnology Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer
Current Medicinal Chemistry