The goal of the Colorado Lung Cancer SPORE program is to conduct translational research studies that will lead to a reduction in the lung cancer mortality rates through improved early detection, prevention, and treatment. This goal is accomplished through four novel projects, a developmental research program, and a career development program all of which are supported by four interacting shared core resources. The future impact of the program will be to hasten translation of scientific discoveries from their development to approved human use of products and services benefiting patients. The projects proposed for this next cycle are Targeting FGFR Signaling in Lung Cancer (Proj. 1); Improving the Outcome of EGFR TKI Therapy Using Rational Combinations (Proj. 2); Prostacyclin and Peroxisome Proliferator-Activated Receptor-y in Lung Cancer (Proj. 3); and Predictors of Pulmonary Nodule Malignancy (Proj. 4). The proposed shared core resources are a Tissue Bank and Biomarkers Core (A); Clinical Trials Core (B); Biostatitistics/Bioinformatics/lnformatics Core (C); and Administrative Core (D). Each Core will facilitate the translation of the research conducted by the Projects. Our SPORE studies have already had a strong impact by contributing to a transformation in the way high risk subjects and lung cancer patients are approached and treated. We are proud of our role in: 1) the development and approval of EGFR TKI therapy coupled with predictive mariners for patient selection; 2) the approval of crizotinib and the use of the FISH break-apart probe as a predictive biomarker; 3) the use of etinostat (HDAC inhibitor) for improving outcome of EGFR TKI therapy; 4) the huge potential of low dose spiral CT screening to reduce lung cancer mortality, especially if barriers can be overcome; 5) changing the landscape of chemoprevention trials allowing rapid completion of moderately sized trials and the potential for a major national randomized phase III trial. We believe that our SPORE studies and collaboration have played a key role in the transformation of lung cancer diagnosis and therapy and that our proposed studies will be equally effective in bringing new products and approaches to lung cancer patients. We believe that we can continue our success in the next grant cycle with translation of discovery to early SPORE trials and handoff of more advanced discoveries to industry and cooperative groups.