Mutation of a gene involved in non-small cell lung cancer (NSCLC) increases the likelihood that the drug gefitinib (Iressa™) will show a beneficial response, researchers at the Dana-Farber Cancer Institute, the National Cancer Institute (NCI) - part of the National Institutes of Health - and two other institutions announced today in the online version of Science. Previously, gefitinib had been shown to cause tumor regression in certain patients, but researchers had not been able to predict which patients would be responsive to the drug. With this discovery, doctors will be able to select those lung cancer patients who could most benefit from gefitinib and may identify additional patients with other types of cancer who may respond to similar treatments.
The mutation discovered was in the epidermal growth factor receptor (EGFR), a gene that codes for an enzyme in the tyrosine kinase family of proteins. Tyrosine kinases are a class of enzymes involved in cellular signaling that have been shown to undergo mutations in various cancers. Inhibition of this type of enzyme has recently been a focus for scientists, but gefitinib had not been as effective as some had expected based on earlier clinical trials conducted in Japan.
The gene mutations identified in this study cause the kinase to be overactive. The sensitivity to gefitinib in both patients entered into a clinical trial and to tumor cells grown in a lab was shown to be highly correlated with the presence of tumors that contained these EGFR mutations. While this type of drug sensitivity was shown earlier for the drug imatinib (Gleevec™), which is most effective against certain leukemias and gastrointestinal stromal tumors that possess specific genetic mutations, this is the first demonstration of a targeted therapy in a common adult malignancy.
"One of the more striking results we found in this study was the difference in response between Japanese and American patients, which raises the question of genetic variation in different ethnic, cultural, and geographic groups to this particular drug," said Bruce E. Johnson, M.D., Dana-Farber Cancer Institute, who led the Lung Cancer Biology Section at NCI before leaving for Dana-Farber.