Mutation In EGFR Gene Makes Lung Cancers Resistant To Gefitinib

NEW YORK (Reuters Health) - Non-small cell lung cancers harboring mutations in the gene for epidermal growth factor receptor (EGFR) show sensitivity to gefitinib. Now, findings from a case report in the February 24th issue of the New England Journal of Medicine indicate that a different mutation in this gene may account for acquired resistance to gefitinib.

The results suggest that a threonine-to-methionine change at position 790 (T790M) of the EGFR gene may arise during gefitinib therapy, rendering cancers resistant to this drug. The same mutation was described earlier this week by a different group of researchers (see Reuters Health report February 22, 2005).

The present report involved a 71-year-old former smoker with adenocarcinoma of the lung. The patient had an EGFR-sensitizing mutation and initially responded well to gefitinib therapy, achieving 2 years of complete remission, senior author Dr. Daniel G. Tenen, from Harvard Medical School in Boston, and colleagues note.

When the patient relapsed, the EGFR gene was again analyzed and this time showed the T790M mutation as well as the initial mutation. Structural modeling and biochemical analysis confirmed that this second mutation was responsible for the gefitinib resistance.

In a related editorial, Dr. Jonathan E. Dowell and Dr. John D. Minna, from the University of Texas Southwestern Medical Center, Dallas, comment that "it will be important to discover at what stage, in the pathogenesis of lung cancer, EGFR mutations occur. If they are found in preneoplastic lesions, it may be possible to screen for them and, if they are present, to use relatively nontoxic tyrosine kinase inhibitors as chemopreventive agents."

Source: N Engl J Med 2005;352:786-792,830-832. [ Google search on this article ]

MeSH Headings: Membrane Proteins : Receptors, Cell Surface : Receptor, Epidermal Growth Factor : Receptors, Gastrointestinal Hormone : Receptors, Growth Factor : Receptors, Peptide