Non-small cell lung cancers (NSCLCs) from patients exhibit large differences in sensitivity or resistance to chemotherapy and targeted drugs. We hypothesize that these differences will be reflected in tumor mRNA and protein signatures prior to treatment, and that these signatures can be used to improve the effectiveness of therapy. The eventual goal to develop and use such signatures to determine the best available treatment for that individual. To move towards this goal, however, there is a critical need for preclinical models to develop such signatures and test new therapies. This project proposes to use a large panel of NSCLC cell lines and xenografts to systematically measure preclinical therapy response phenotypes, define associated mRNA and protein biomarker signatures of these responses, and then validate these in other cell lines, xenografts, and patient tumor specimens. We will also identify mRNA and protein biomarkers in patient specimens and test them in the preclinical models, eventually resulting in validated biomarkers for response prediction in patients and validated preclinical models.
Specific Aims are:
Aim 1) To measure quantitative drug sensitivity/resistance phenotypes in a large panel (-100) of human NSCLC cell lines and xenografts (~50), including xenografts made directly from patient tumors without intervening culture, and compare in vitro drug response phenotypes with those of orthotopic (lung) xenografts;
Aim 2) To identify microarray mRNA and reverse phase protein array (RPPA)-based expression signatures of response to therapeutic agents in NSCLC lines;using these signatures we will predict drug responses in a new

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-I)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
United States
Zip Code
Wen, Chi-Pang; Zhang, Fanmao; Liang, Dong et al. (2015) The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling. Clin Cancer Res 21:193-200
Chiappori, A A; Kolevska, T; Spigel, D R et al. (2015) A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer. Ann Oncol 26:354-62
Mender, Ilgen; Gryaznov, Sergei; Dikmen, Z Gunnur et al. (2015) Induction of telomere dysfunction mediated by the telomerase substrate precursor 6-thio-2'-deoxyguanosine. Cancer Discov 5:82-95
Kim, Eric S; Ye, Yuanqing; Vaporciyan, Ara A et al. (2015) Telomere length and recurrence risk after curative resection in patients with early-stage non-small-cell lung cancer: a prospective cohort study. J Thorac Oncol 10:302-8
Ludlow, Andrew T; Robin, Jerome D; Sayed, Mohammed et al. (2014) Quantitative telomerase enzyme activity determination using droplet digital PCR with single cell resolution. Nucleic Acids Res 42:e104
Fujimoto, Junya; Wistuba, Ignacio I (2014) Current concepts on the molecular pathology of non-small cell lung carcinoma. Semin Diagn Pathol 31:306-13
Yang, Yanan; Ahn, Young-Ho; Chen, Yulong et al. (2014) ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism. J Clin Invest 124:2696-708
Lin, Steven H; Wang, Jing; Saintigny, Pierre et al. (2014) Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial-mesenchymal transition. BMC Genomics 15:1079
Osborne, Jihan K; Guerra, Marcy L; Gonzales, Joshua X et al. (2014) NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas. Mol Biol Cell 25:1782-92
Holohan, Brody; Wright, Woodring E; Shay, Jerry W (2014) Cell biology of disease: Telomeropathies: an emerging spectrum disorder. J Cell Biol 205:289-99

Showing the most recent 10 out of 647 publications