Memorial Sloan-Kettering Cancer Center investigators have created two new mouse models of lung adenocarcinoma. The models were developed based on previous studies carried out at Memorial Sloan-Kettering and elsewhere that identified mutations in the epidermal growth factor receptor (EGFR) gene in approximately 10 percent of US cases of lung adenocarcinoma, the most common form of lung cancer. Mutations in EGFR are associated with a response to the targeted therapies gefitinib (Iressa®) and erlotinib (Tarceva®).

The mouse models, developed by postdoctoral research fellow Katerina Politi and colleagues working in the laboratory of Memorial Sloan-Kettering President and Faculty Member Harold Varmus, were genetically engineered to carry the two most common classes of EGFR mutations, such that the mutant genes could be turned on or off by the presence or absence of the antibiotic doxycycline in the mouse's diet. Turning on expression of either EGFR mutant caused tumors to form in the mice, and turning off the genes caused tumors to regress. Treatment of these mice with the drug erlotinib also caused the tumors to regress, indicating that this system closely recapitulates human disease.

"These new mouse models can now be used to further understand the molecular basis of mutant EGFR-driven oncogenesis and to test potential new lung cancer drugs," Dr. Politi said. The research was published in the June 1 issue of Genes & Development. [PubMed Abstract]