TARGETING THE PROSTACYCLIN/PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA AXIS IN LUNG CANCER CHEMOPREVENTION.

ABSTRACT

Lung cancer remains an important target of cancer research, and accounts for most deaths of any cancer type in the United States. Chemoprevention refers to the use of agents to prevent the development of cancer in high-risk populations, often in patients with predisposing lesions. In the following, we describe our ongoing work examining the role of the eicosanoid prostacyclin in lung cancer chemoprevention. Our findings include the fact that most adenocarcinomas lose the expression of prostacyclin synthase through methylation silencing. In addition, transgenic mice with overexpression of prostacyclin synthase are protected from tumorigenesis in multiple preclinical lung cancer models. Our phase IIb clinical trial using iloprost, a prostacyclin analogue, showed the reversal of airway dysplasia in high-risk individuals. This trial represents the first to show regression of airway dysplasia from the administration of a chemoprevention agent and forms the basis for future trials in lung cancer chemoprevention.