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.
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.
|Scarborough, Hannah A; Helfrich, Barbara A; Casás-Selves, Matias et al. (2017) 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 23:1531-1541|
|Harder, Bryan; Tian, Wang; La Clair, James J et al. (2017) Brusatol overcomes chemoresistance through inhibition of protein translation. Mol Carcinog 56:1493-1500|
|Chen, Yufei; Anastassiadis, Konstantinos; Kranz, Andrea et al. (2017) MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell 31:755-770.e6|
|DeRyckere, Deborah; Lee-Sherick, Alisa B; Huey, Madeline G et al. (2017) UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models. Clin Cancer Res 23:1481-1492|
|Todd, Maria C; Langan, Thomas A; Sclafani, Robert A (2017) Doxycycline-Regulated p16MTS1 Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16. J Cancer 8:190-198|
|Neelakantan, Deepika; Zhou, Hengbo; Oliphant, Michael U J et al. (2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773|
|Barón, Anna E; Kako, Severine; Feser, William J et al. (2017) Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer. J Thorac Oncol 12:1512-1523|
|Shearn, Colin T; Saba, Laura M; Roede, James R et al. (2017) Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. Free Radic Biol Med 113:280-290|
|Brown, Dustin G; Borresen, Erica C; Brown, Regina J et al. (2017) Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial. Br J Nutr 117:1244-1256|
|Haverkos, Bradley M; Abbott, Diana; Hamadani, Mehdi et al. (2017) PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 130:221-228|
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