The drugs are so-called kinase inhibitors and inhibit the epidermal growth factor receptor (EGFR) kinase molecule. Both of them, gefitinib (Iressa) and erlotinib (Tarceva), have shown therapeutic benefits in a subset of patients with lung cancer. Recent work has helped to understand why some patients respond and some don't: responsive tumors usually harbor activating mutations in the EGFR gene, which somehow make the tumors sensitive to treatment. Nearly all patients whose tumors initially respond to the drugs, however, eventually become resistant to the drugs and progress despite continued therapy.
In this study, the scientists examined tumors from six patients with non-small cell lung cancer who initially responded to gefitinib or erlotinib but subsequently relapsed. Tumors from all six patients carried activating mutations in the EGFR gene. In addition, in three out of the six cases, the resistant tumor cells carried an identical second mutation in the EGFR gene. Whereas the activating mutation was present in tumor cells before treatment with erlotinib or gefitinib, the second mutation was not found in pre-treatment biopsies from these patients, nor in over 150 lung cancer samples from patients who had not been treated with either drug. Additional cell culture studies supported the notion that the secondary mutation causes resistance to gefitinib or erlotinib. It is clear, though, that this is only one of several resistance mechanisms, because in the three other cases
Contact: Paul Ocampo
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