Lung cancer is the leading cause of cancer-related deaths worldwide. Based on status quo detection strategies and therapies, only 16% of patients diagnosed last year with lung cancer will survive for five years. Lung cancer is the result of a wide range of genetic changes, many of which indirectly affect protein kinase signaling pathways that disrupt the normal homeostasis of cell proliferation and apoptosis. Protein kinases are now an important class of targets for lung cancer therapy. The purpose of the experiments proposed here is to develop and validate quantitative methods in phosphoproteomics capable of probing differences in cellular signaling in lung tumors that correlate with patient outcomes. To do this, we will i) develop a quantitative phosphoproteomics technology for clinical lung cancer specimens, ii) develop phospho-multiple reaction monitoring (p-MRM) methods that target substrates of clinically relevant kinases, and iii) deploy these methods to study differences in cellular signaling in tumors from a limited cohort of non-small cell lung cancer patients. We anticipate that the successful conduct of the experiments proposed here will provide translational scientists and thoracic oncologists with an entirely new dimension of biomedical information which will enable the discovery of new treatment strategies, improve assessments of patient responsiveness to kinase inhibitor therapies at the molecular level, and allow for highly individualized decisions regarding patient care.

Public Health Relevance

Lung cancer is the leading cause of cancer-related deaths worldwide. By developing new approaches to look at how cellular signals correlate with the outcome of disease, the research presented here is designed to accelerate the clinical discovery and validation of new therapeutic strategies for the treatment of lung cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA155260-03
Application #
8513273
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Kim, Kelly Y
Project Start
2011-09-02
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$308,179
Indirect Cost
$113,129
Name
Dartmouth College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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