Mouse models of Lung Adenocarcinoma : Steps towards Personalized treatment of cancer.

Abstract : Lung Cancer is the single leading cause of cancer deaths around the world.We generated mouse models of lung adenocarcinoma using lentiviral vectorsto deliver oncogenes and hairpins to tumorsuppressors. We showed NF-kappaBpathway regulates proliferation in lung adenocarcinoma by upregulating TIMP1. Further, we employed an in vivo shRNA screen to identify novel tumorsuppressors. The screen identified several tumorsuppressors including a receptor tyrosine kinase, Ephrin receptor A2. Knockdown of EphA2 cooperates with oncogenic KRasG12D expression. Loss of EphA2 promotes tumorigenesis by activating multiple oncogenic signaling pathways.Lentiviral mouse models provide an important method to test mutations and copy number variations that are found in cancer genomes of lung adenocarcinoma patients. Further high throughput screens using CRISPR/gRNA mediated gene deletion will discover novel cancer vulnerabilities and therapeutic modalities. Long-term focus of our research is to model patient specific mutations and copy number variations and discover vulnerabilities to find patient specific therapeutic approaches.