Lung cancer is the leading cause of cancer related deaths in the United States. Radiation therapy, either alone or in combination with systemic chemotherapy, is one of the main treatment modalities for locally advanced non-small cell lung cancer (NSCLC). Recently, driven by a better understanding of the molecular oncogenic drivers involved in lung tumorigenesis, targeted systemic therapies have been developed clinically to generate higher response rates and longer overall survival in a genetically stratified population of lung cancer patients. For example, erlotinib and gefitinib have produced up to 85 percent response rates and longer overall survival in patients with NSCLC who harbor selective EGFR kinase domain (KD) mutations when compared to conventional chemotherapies. However, our understanding of how specific oncogenic drivers in NSCLC impact their sensitivity to radiation therapy or combination chemo-radiation therapy is limited and has not been systematically studied in vivo pre- clinically. In this proposal, as outlined in the specific aims below, we propose to employ our well characterized genetically engineered mouse models of lung cancer based on inducible lung epithelium specific expression of the common lung cancer relevant oncogenic drivers (EGFR kinase domain mutants, EGFRvIII mutant and KRAS mutants) along with the latest small animal focal irradiator platform to dissect the differential sensitivity of the defined oncogene driven lung cancer to radiation therapy and combined chemo-radiation therapy in vivo. Data from the successful completion of the aims will help facilitate the identification of genotype specific lung cancers that are radiosensitive, help rationally integrate radiation therapy with targeted therapeutics and, thus, advance the care and treatment of lung cancer patients.

Public Health Relevance

Lung cancer is the leading cause of cancer related deaths in the United States. Experiments proposed in this grant will help identify genetic subtypes of lung cancers that are sensitive to radiation treatment, and thus, help advance the care and treatment of lung cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA122794-07
Application #
8332284
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Forry, Suzanne L
Project Start
2006-07-31
Project End
2016-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
7
Fiscal Year
2012
Total Cost
$282,228
Indirect Cost
$109,875
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
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