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

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA070907-15W1
Application #
8731332
Study Section
Special Emphasis Panel (ZCA1-GRB-I)
Project Start
2013-09-12
Project End
2014-08-31
Budget Start
2013-09-12
Budget End
2014-08-31
Support Year
15
Fiscal Year
2013
Total Cost
$156,620
Indirect Cost
$38,357
Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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