A Preclinical Model for Mutant Human EGFR-driven Lung Adenocarcinoma

Abstract:

Previously described epidermal growth factor receptor- (EGFR) driven tumor mouse models develop diffuse tumors, which are dissimilar to human lung tumor morphology and difficult to measure by CT and MRI scans. Scientists at the National Cancer Institute (NCI) have developed and characterized a genetically engineered mouse (GEM) model of human EGFR-driven tumor model (hEGFR-TL) that recapitulates the discrete lung tumor nodules similar to those found in human lung tumor morphology. Individual tumor nodules can be easily measured by live animal imaging and the nodules can be harvested and isolated from surrounding lung tissue post-treatment, making this a more tractable model for human non-small cell lung adenocarcinoma. The lungs express an EGFR transgene that harbors two mutations (‘L858R’ and ‘T790M’) which render the lung tumors resistant to first generation EGFR inhibitors and are useful for evaluating drugs targeting resistant tumors.

Competitive Advantages:

• Lung tumor development and response to drugs can be monitored by MRI or CT scanning
• Contain a human EGFR transgene (either TRE-EGFR-L858R or TRE-EGFR-L858R-T790M models are available) and an activating transgene (CCSP-rtTA) to direct expression of mutant EGFR to the Clara cells

Commercial Applications:

• Preclinical in vivo screen of therapeutics targeting tumor kinase inhibitors such as EGFR-mediated lung tumors, and identification of new biomarkers in this pathway 
• Evaluation of novel therapeutics in inducible models of EGFR-driven drug resistant lung adenocarcinoma
• Dermatology Research
• Immunology, Inflammation and Autoimmunity Research