This is one of a series of articles relating to tetrathiomolybdate, which is used against Wilson's disease:
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15892619
1: Curr Cancer Drug Targets. 2005 May;5(3):195-202.
Copper lowering therapy with tetrathiomolybdate as an antiangiogenic strategy in cancer.
Brewer GJ.
Department of Human Genetics, University of Michigan Medical School, 5024 Kresge
Bldg. II, Ann Arbor, MI 48109-0534, USA.
brewergj@umich.edu
Tetrathiomolybdate (TM) is a novel anticopper agent under development for use in Wilson's 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. TM's 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 (NF(K)B), 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 angiogeniccytokines gives TM the potential to be a more global inhibitor of angiogenesis.
PMID: 15892619 [PubMed - indexed for MEDLINE]