Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a review.
A new anticopper drug, tetrathiomolybdate (TM), developed for Wilson's disease, is a very promising antiangiogenic agent. Copper levels lowered into an antiangiogenic window by TM have shown efficacy against cancer in a variety of animal models as well as in patients. The only significant toxicity so far results from overtreatment and excessive bone marrow depletion of copper. The resulting anemia and/or leukopenia is easily treatable by dose reduction or drug holiday. The underlying concept for TM efficacy as an anticancer agent is that when the body's copper status is in the window, cellular copper needs are met and toxicity is avoided. Copper status is relatively easily monitored by following serum ceruloplasmin, a copper-containing protein secreted by the liver at a rate dependent upon the amount of copper in the liver available to incorporate into the protein. The authors speculate that the copper level is a primitive angiogenesis and growth-signaling regulator that has been retained throughout evolution.
Brewer
George J
GJ
Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, 4009 Buhl Building, Ann Arbor, MI 48109-0618, USA. brewerj@umich.edu
Merajver
Sofia D
SD
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D003300:Copper / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008982:Molybdenum / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D002614:Chelating Agents; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate