Copper lowering therapy with tetrathiomolybdate produces antiangiogenic, anticancer, antifibrotic, and antiinflammatory effects

Tetrathiomolybdate (TM) has been developed to fill an important niche in the initial treatment of Wilson’s disease. TM is a potent, fast-acting, non-toxic anticopper agent. Copper appears to be required for activity of many angiogenic factors, which has led to the trial of TM as an antiangiogenic, anticancer drug. Positive results have been obtained in several animal tumor models, and results are encouraging in early clinical work. TM may be a more global antiangiogenic agent than most agents being developed because many angiogenic factors seem to be copper dependent in some manner. The main toxicity of TM is overtreatment bone marrow suppression. Most recently, TM has been shown to inhibit important profibrotic and proinflammatory cytokines, and preclinical status of TM therapy has been positive in lung and liver models of inflammation and fibrosis.