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Laboratory study explains clinical promise of anti-angiogenesis cancer drug

ANN ARBOR, MI For nearly five years, doctors at the University of Michigan Comprehensive Cancer Center have noted promising cancer-slowing results from early clinical trials of a drug that lowers the level of copper in cancer patients' blood.

Now, new U-M laboratory research results are telling them exactly how that experimental drug works, and showing them its cancer-fighting potential on a cellular level. The findings, published in the current issue of the journal Cancer Research, have implications for the approach to cancer treatment known as anti-angiogenesis.

The paper describes how the drug -- tetrathiomolybdate, or TM -- keeps tumor cells from sending signals that spur the formation of new blood vessels. By keeping copper low and blocking the NFkB signaling pathway, the researchers believe, TM blocks the angiogenesis, or blood-vessel creation, that lets cancer grow and spread.

Angiogenesis is thought to be a common denominator for many kinds of cancer, allowing tumors to grow locally and to metastasize to the rest of the body. The U-M team explored TM's anti-angiogenic potential using four methods in mice and cells.

Specifically, they showed that TM suppressed the growth of tumors in mice implanted with cells from an aggressive form of human breast cancer; kept new blood vessels from forming in cancer-prone cultures of rat artery cells; squelched the release of a key signaling molecule known to spur blood vessel formation; and prevented the formation of tumors in mice specially bred to develop breast cancer.

"Taken together, these results support the initial findings of the clinical trials that have been done with TM, and indicate that copper reduction can inhibit tumor angiogenesis with minimal adverse effects," says senior author Sofia D. Merajver, M.D., Ph.D., associate professor of internal medicine and director of the U-M Breast and Ovarian Cancer Risk Evaluation Program. She notes that the copper reduction achi
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
6-Sep-2002


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