BOSTON -- Dana-Farber Cancer Institute researchers and their colleagues have demonstrated that a genetic error so scarce it can't be detected with some standard screening equipment is often responsible for the loss of effectiveness of front-line drugs against non-small cell lung cancer.
Investigators led by Pasi Jnne, MD, PhD, found that many non-small cell lung cancer (NSCLC) patients who become resistant to targeted drugs such as Iressa and Tarceva have a mutation in a single building block of the EGFR protein. The study, which currently is published online by the Journal of Clinical Investigation, demonstrates that even a minute mutation, present in tiny quantities, is sufficient to cause drug resistance in some cancers. The findings will be published in the journal's October print edition.
"The implication of our study is that perhaps many more patients than previously thought have this as their mechanism of resistance," says Jnne. "Identifying those patients will be important in the next generation clinical studies of drugs for NSCLC, which accounts for about 85 percent of all cases of lung cancer in the United States."
Iressa and Tarceva are used to treat NSCLC in patients whose cancer cells have abnormalities in the EGFR gene. It's estimated that 10-15 percent of NSCLC patients in the U.S. have such mutations, and up to 40 percent of those in Asia. In virtually all cases, however, the drugs lose their effectiveness with time between six and 14 months, depending on the type of mutation a patient has.
Scientists have suggested that about half of NSCLC patients who develop resistance to Iressa-like drugs have a specific mutation in one of the chemical components of EGFR amino acid 790 (designated T790M) but it wasn't known whether this secondary mutation was enough to cause the resistance. To find out, Jnne and his colleagues did an experiment involving NSCLC cells from patients who responded well to Iressa. Research
Contact: Bill Schaller
Dana-Farber Cancer Institute