Chemoprevention of Lung Cancer

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Lung cancer is the leading cause of death in men and women in the United States (160,000 new cases and 157,400 deaths in 2001). Although the relative risk of developing lung cancer declines in smokers who quit, former smokers remain at high risk for at least 5 years. Since smoking cessation is a major public health initiative, former smokers will increasingly account for a high percentage of lung cancer. A potential important approach to reduce the large number of tobacco caused cancer deaths is chemoprevention. The long-term goal o f our Chemoprevention of Lung Cancer Program Project is to develop chemopreventive strategies to reduce the incidents of lung cancer in high-risk current and former smokers. The Program Project will focus its chemoprevention strategies on Budesonide (a glucocorticoid agonist), green tea extracts (Polyphenon E), Myo-inositol, and difiuoromethylornithine (DFMO) for three reasons: i) they exhibit high chemopreventive efficacy in rodent models; ii) they are effective in the post-initiation period of carcinogenesis; and iii) they have a previous history of therapeutic or dietary administration to humans. Our Program Project consists of four research projects designed by a group of lung cancer scientists to address our primary hypothesis--selective combination of chemoprevention agents can prevent the progression and formation ofpreneoplastic lesions in the respiratory epithelium. In summary, the Program Project will (1) conduct a Phase II trial to determine the efficacy and safety of green tea, the second most commonly consumed beverage after water for chemoprevention of lung cancer (Project I); (2) generate new information on the use of markers in cell survival pathways as intermediate endpoint biomarkers for chemoprevention trials (Project I-III); (3) facilitate a major new initiative to develop confocal miscroendoscopy as a non-biopsy method to assess the effect ofchemopreventive agents (Project I); (4) determine the scientific basis for combining chemopreventive agents in future Phase II trials by examining their ability to inhibit progression of preneoplasia to more advanced lesions in a mouse model for adenocarcinoma and a hamster model for upper respiratory squamous cell carcinoma (Project II-IV) and by clinical trials with single agents (Project I).