Lung and head and neck cancer (HNC) are the leading cause of cancer death and the most psychologically distressing cancer, respectively;both are largely tobacco induced. The overall goal of the Lung, Head and Neck (LHN) Program is to translate fundamental scientific research discoveries into preventive and therapeutic interventions and thereby decrease the incidence and mortality of lung and HNC. These goals are achieved by fostering collaborations between scientists focused on population, behavioral, basic, clinical, therapeutic and translational studies. The LHN Program has 3 focus groups: 1) Risk Biomarkers, Early Detection and Prevention. 2) Tumor Genetics and Biology. 3) Experimental Therapeutics. In one strategy to accomplish our goal, our members are developing genetically engineered mouse models to characterize LHN-specific genetic aberrations and test novel chemopreventive strategies and targeted therapies in a setting of naturally occurring spontaneous cancer. These are complemented by direct patient tumor xenograft models to test personalized targeted therapies. Tumors developed from these models together with primary patient samples are subjected to high throughput genetic/epigenetic/protein analyses for discovery of prognostic and predictive biomarkers. Research using these cutting-edge models has and will continue to translate into investigator-initiated clinical trials that incorporate clinical biomarkers. In the previous funding period the program made several major contributions to the field including: 1. The first Phase II chemoprevention trial to demonstrate improvement in endobronchial dysplasia (Iloprost trial);2.Development of biomarkers to predict sensitivity to EGFR and ALK TKIs;3. Development of genetically engineered mouse models for HNC;4. Development and validation of biomarkers of lung cancer risk and diagnosis, and;5. Fundamental research leading to a trial of EGFR and HDAC inhibition. LHN consists of 31 Full members from 11 departments in 6 schools at 4 consortium institutions. Members currently hold $5.2M in NCI grant support and $11.5M in other cancer relevant research support. Per capita cancer research funding has increased by 88% from $287K in 2005 to $539K in 2010. Over the same period, LHN members produced 380 cancer-related publications of which 101 (27%) were interprogrammatic; 38 (10%) were intra-programmatic and 101 (27%) were both inter- and intra-programmatic for a total of 240 (63%) collaborative publications.

Public Health Relevance

Lung and head and neck cancer are the leading cause of cancer death and the most psychologically distressing cancer, respectively. Both are largely tobacco induced, affect the respiratory tract and share many biologic features. The LHN Program moves basic science findings to clinical practice, exemplified by the discovery of predictive biomarkers to guide therapeutic strategies, early detection and prevention advances and the use of genetic models of cancer to understand the biology of these malignancies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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University of Colorado Denver
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McCubbrey, Alexandra L; Barthel, Lea; Mohning, Michael P et al. (2018) Deletion of c-FLIP from CD11bhi Macrophages Prevents Development of Bleomycin-induced Lung Fibrosis. Am J Respir Cell Mol Biol 58:66-78
Fitzpatrick, Rikki L; Quimby, Jessica M; Benson, Kellyi K et al. (2018) In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease. J Vet Intern Med 32:1951-1957
Lee, Kyubum; Kim, Byounggun; Choi, Yonghwa et al. (2018) Deep learning of mutation-gene-drug relations from the literature. BMC Bioinformatics 19:21
Roof, Allyson K; Jirawatnotai, Siwanon; Trudeau, Tammy et al. (2018) The Balance of PI3K and ERK Signaling Is Dysregulated in Prolactinoma and Modulated by Dopamine. Endocrinology 159:2421-2434
Kimball, Abigail K; Oko, Lauren M; Bullock, Bonnie L et al. (2018) A Beginner's Guide to Analyzing and Visualizing Mass Cytometry Data. J Immunol 200:3-22
Parrish, Janet K; McCann, Tyler S; Sechler, Marybeth et al. (2018) The Jumonji-domain histone demethylase inhibitor JIB-04 deregulates oncogenic programs and increases DNA damage in Ewing Sarcoma, resulting in impaired cell proliferation and survival, and reduced tumor growth. Oncotarget 9:33110-33123
Herbst, Roy S; Redman, Mary W; Kim, Edward S et al. (2018) Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol 19:101-114
Johnson, Monica; Alsaleh, Nasser; Mendoza, Ryan P et al. (2018) Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms. PLoS One 13:e0193499
Nemkov, Travis; Sun, Kaiqi; Reisz, Julie A et al. (2018) Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage. Haematologica 103:361-372
Soontararak, Sirikul; Chow, Lyndah; Johnson, Valerie et al. (2018) Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model. Stem Cells Transl Med 7:456-467

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