The chemopreventive effect of an aerosolized rexinoid, bexarotene, and its efficacy in all subtypes of lung cancer, will be examined using a state-of-the-art (Collison atomizer) aerosol delivery system to lung to avoid the systematic side effects associated with oral administration of this agent. Bexarotene has been used clinically to treat cutaneous T cell lymphoma in patients who were refractory to any other medication. Bexarotene has also shown efficacy in a Phase 1/2 trial of non-small cell lung cancer (NSCLC). It is the only agent tested to date that is highly effective in mouse models of adenocarcinoma, squamous cell carcinoma (SCC), and SCLC. In B[a]P-induced lung tumors in A/J mice, aerosolized delivery of bexarotene retained lung tumor inhibitory effects without increasing plasma total cholesterol and triglyceride levels, compared with control. The proposed project will study aerosolized bexarotene in mouse models of both SCC and SCLC, as well as its effects on tumor progression (from benign to malignant tumors) in mouse models of lung adenocarcinoma, while closely monitoring side effects and toxicity. The project will also analyze changes in cell proliferation markers (cyclin D1 and Ki- 67), apoptotic activity, and infiltrating lymphoid cells, as well as mRNA changes in lung tumors and surrounding lung tissues.