As reported in the June 1 issue of G&D, Drs. Katerina Politi, Harold Varmus and colleagues at the Memorial Sloan Kettering Cancer Center in New York have developed a novel animal model of lung adenocarcinoma that will be of great use in testing the efficacy of targeted therapies against human lung cancer.

"We hope to use these models to understand how mutations in the EGFR gene initiate lung tumors, which are the most common cause of cancer mortality . In addition, these models will allow us to evaluate the effectiveness of new drugs and drug combinations and to study the molecular basis of resistance to existing tyrosine kinase inhibitors," explains Dr. Politi.

Lung cancer patients who harbor mutations in the human epidermal growth factor receptor (EGFR) gene generally have a better response to drugs that inhibit EGFR (like Iressa and Tarceva). Dr. Politi and colleagues have engineered a strain of mice with a mutated form of EGFR that can be turned on or off in lung cells at will. These inducible EGFR-mutant mice allow the researchers to evaluate the contribution of EGFR mutations to lung cancer formation, progression and response to chemotherapeutics.

The researchers found that mutations in EGFR drive lung tumorigenesis, and that either turning off the mutant EGFR gene or inhibiting it with drug can effectively force the tumors into regression. Thus, their model not only lends mechanistic insight into the genetic factors involved in lung cancer, but also serves as a paradigm to develop, test, and hopefully improve targeted cancer therapies.

Heather Cosel
coselpiecshl.edu
Cold Spring Harbor Laboratory
cshl

View drug information on Iressa; Tarceva.