( BETHESDA Md. April 1 2007--Rapamyci...)Immunosuppressant Drug Prevents Tobacco Induced Lung Cancer in Mice,Health

BETHESDA, Md., April 1, 2007--Rapamycin, an FDA-approved drug normally used to help prevent the body from rejecting organ and bone marrow transplants and also used to coat cardiac stents, was highly effective in preventing the development of tobacco-related lung tumors in mice. In a study published in the April 1, 2007 issue of Clinical Cancer Research, researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, found that mice that were administered rapamycin one week after exposure to a very common tobacco-specific carcinogen showed a 90 percent decrease in the number of tumors, a 74 percent decrease in tumor size, and fewer abnormalities within their cancer cells. The scientists work also shows that mTOR, a protein targeted by rapamycin, plays a critical role in the early stages of development of certain lung tumors caused by tobacco exposure.

We estimate that there will be over 160,000 deaths from lung cancer this year, and 90 percent of those will be attributed to smoking. Quitting smoking reduces lung cancer risk by about 50 percent, said NCI Director John E. Niederhuber, M.D. By exploring methods of chemoprevention via agents such as rapamycin, we may be able to further reduce lung cancer risk.

Previous studies in mice have shown that nicotine and its metabolic byproduct, known as NNK, stimulate the activity of two proteins, Akt and mTOR, in normal cells that line the airways in the lungs. This activation makes the cells pre-cancerous. In addition, clinical studies have shown that Akt is activated in the majority of pre-cancerous lesions in smokers, and that Akt activation predicts shorter survival for non-small cell lung cancer patients, particularly for those in early stages or with small tumors. These studies suggested that Akt and mTOR are important elements in the formation and maintenance of tobacco-carcinogen induced lung tumors, and that targeting
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