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Chemoprevention of Lung Cancer in Transgenic Mice

Chemoprevention of Lung Cancer in Transgenic MiceLung cancer is the leading cause of cancer deaths in men and women in the United States. Epidemiologic and laboratory animal model studies have demonstrated that smoking and environmental exposure to carcinogens are closely linked to increased lung cancer risk. Tobacco exposure has been implicated in 90% of lung carcinomas, and smokers have a 20-fold greater risk of acquiring lung cancer compared with persons who have never smoked. Although approximately one half of all people who had ever smoked are now former smokers, many people are unable or unwilling to stop smoking. For these reasons, chemoprevention is a potentially important approach to reduce the large number of tobacco-caused cancer deaths, especially for former smokers. Chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer.

A primary mode of chemopreven-tion action includes reversing the progression of prema-lignant cells by stimulation of the cell to repair DNA or other cell damage that initiates carcinogenesis. Numerous studies have found chemoprevention methods can prevent or improve the outcome of a wide variety of cancer. This approach is especially useful in targeting persons at high risk for cancer, such as patients who have a genetic predisposition to cancer, or patients who are at high risk for secondary primary tumors after surgical removal of a tumor. The targets for pharmacologic intervention are the various stages of tumor development, including hyperplasia and dysplasia. There are two major classes of cancer chemopreventive agents: blocking agents and suppressing agents. Blocking agents prevent metabolic activation of carcinogens to reduce the likelihood of DNA damage. Suppressing agents can block expansion of carcinogen-initiated cells by suppressing cell replication or by causing apoptosis of precancerous or cancerous cells.