Grants - Translational Grants - Colorado - 2017

York Miller, M.D., Moumita Ghosh, Ph.D., & Jihye Kim, Ph.D.

Lung cancer is the leading cause of cancer death in the US and worldwide with 15-18% cure rate. Thus, prevention is a critical strategy to decrease lung cancer deaths. Tobacco smoking causes the large majority of lung cancer and smoking cessation is the best intervention in smokers; however, the risk of lung cancer in former smokers remains high. The administration of drugs or natural products to prevent cancer is called chemoprevention. Unfortunately, currently, no drug, natural product or vitamin has been shown to decrease lung cancer incidence in humans.

The prostacyclin analog, iloprost, prevents lung cancer in mice exposed to tobacco smoke, as well as other chemicals. Therefore, we performed an early phase clinical trial of iloprost in humans. Iloprost improved airway changes that lead to lung cancer in humans, but only in former, not current, smokers. 59% of former smokers given iloprost improved airway dysplasia compared to 29% given placebo. Our goal is to be able to identify those former smokers who will benefit from iloprost so as to treat the right patients with the right drug. We have developed a patient-derived epithelial progenitor cell culture that can lead to such a test, as it recapitulates the morphologic improvement in dysplasia. Preliminary data suggest that gene expression differs between iloprost responders and non-responders at baseline. If we can develop a biomarker to discriminate responders from non-responders, future clinical trials can be accelerated and if positive, iloprost chemoprevention can be targeted to the correct subset of former smokers.

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