Responsiveness to Cetuximab without Mutations inEGFR

T790M mutation was shown to confer resistance to gefitinib after it was introduced into the sequence of the wild-type EGFR and L858R mutant EGFR in vitro. 2,3 The T790M mutation results in steric hindrance of binding of gefitinib to the ATPkinase-binding pocket.The T790M mutation may cause acquired resistance to gefitinib. 2,3Our patient had concomitant T790M and L858R EGFR mutations in the original lung-biopsy specimen and showed primary resistance to gefitinib -a finding implying that a mutation in the T790M kinase domain can occur during the natural evolution of lung cancer.T790M mutant gefitinibresistant clones may preexist at levels below the threshold of detection 5 in some patients with lung cancer at presentation and then may expand selectively under gefitinib treatment, leading to the failure of gefitinib therapy.