The overarching goal of the project is to discover and translate knowledge regarding the biology of pulmonary premalignancy to reduce lung cancer burden through 1) the discovery and validation of clinically useful biomarkers of risk and 2) the development of effective chemopreventive treatments. Biomarkers of lung cancer risk can have a variety of clinical uses, including population screening for early detection, defining high risk populations and as aids in guiding clinical decision making in settings of CT detected nodules of indeterminate etiology. Regardless of the outcome of ongoing randomized controlled trials of lung cancer screening using CT, there will be an increasing clinical need for risk biomarkers to guide decisions on management of lung nodules detected by CT. New knowledge regarding the biology of pulmonary premalignancy is being translated to novel chemoprevention strategies by this and other SPORE projects.
Our Specific Aims are to:
Specific Aim 1. Identify and validate biomarkers of lung cancer in sputum, bronchial epithelium, BAL and blood. We will focus on biomarkers with considerable preliminary support, including atypia, gene promoter hypermethylation and chromosomal aneusomy in sputum, as well as on the development of new approaches, including these same markers and protein expression in bronchial epithelium and bronchoalveolar lavage. We will take advantage of unique prospective cohorts of subjects with biological samples harvested and stored and in whom both prevalent and incident lung cancer is tracked by a team of epidemiology staff to carry out cross sectional and longitudinal nested case control studies.
Specific Aim 2. Validate the clinical utility of sputum biomarkers in the context of the NLST ACRIN Trial. The most promising sputum markers from Specific Aim 1 will be validated as a complementary set of biomarkers in groups of subjects strategically defined and sampled from a trial of CT screening. Analyses will assess the performance of this biomarker panel for lung cancer screening as well as for its utility in assisting in clinical decisions regarding the management of pulmonary nodules of undetermined significance.
Specific Aim 3. Conduct Phase II chemoprevention trials to prioritize agents for testing in Phase III trials. The current lloprost chemoprevention trial will be completed in early 2008. We will analyze the response and develop a successor trial based on a PPAR gamma agonist as supported by preclinical data from Project 3. Our proposal will have important implications for early detection, diagnosis and prevention of lung cancer

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA058187-18W1
Application #
8719574
Study Section
Special Emphasis Panel (ZCA1-GRB-I)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
18
Fiscal Year
2013
Total Cost
$123,331
Indirect Cost
$43,315
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Symonds, Jennifer M; Ohm, Angela M; Tan, Aik-Choon et al. (2016) PKCδ regulates integrin αVβ3 expression and transformed growth of K-ras dependent lung cancer cells. Oncotarget 7:17905-19
Dziadziuszko, Rafal; Le, Anh T; Wrona, Anna et al. (2016) An Activating KIT Mutation Induces Crizotinib Resistance in ROS1-Positive Lung Cancer. J Thorac Oncol 11:1273-81
Saichaemchan, S; Ariyawutyakorn, W; Varella-Garcia, M (2016) Fibroblast Growth Factor Receptors: From the Oncogenic Pathway to Targeted Therapy. Curr Mol Med 16:40-62
Scarborough, Hannah A; Helfrich, Barbara A; Casas-Selves, Matias et al. (2016) AZ1366: An inhibitor of tankyrase and the canonical Wnt pathway that limits the persistence of non-small cell lung cancer cells following EGFR inhibition. Clin Cancer Res :
Poczobutt, Joanna M; Nguyen, Teresa T; Hanson, Dwight et al. (2016) Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment. J Immunol 196:891-901
Li, Bob T; Ross, Dara S; Aisner, Dara L et al. (2016) HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers. J Thorac Oncol 11:414-9
Yoshida, Takeshi; Song, Lanxi; Bai, Yun et al. (2016) ZEB1 Mediates Acquired Resistance to the Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. PLoS One 11:e0147344
Ariyawutyakorn, Witthawat; Saichaemchan, Siriwimon; Varella-Garcia, Marileila (2016) Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet? J Cancer 7:633-49
Bunn Jr, Paul A; Minna, John D; Augustyn, Alexander et al. (2016) Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? J Thorac Oncol 11:453-74
Helfrich, Barbara A; Kim, Jihye; Gao, Dexiang et al. (2016) Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo. Mol Cancer Ther 15:2314-2322

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