Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non-Small Cell Lung Cancer Cell Line

摘要: The epidermal growth factor receptor (EGFR)–specific tyrosine kinase inhibitor gefitinib may provide dramatic clinical responses in some patients with pulmonary adenocarcinoma carrying activating mutations of the EGFR. However, prolonged administration eventually induce acquired resistance such patients. To gain insight into mechanisms this phenomenon, we placed PC-9, a cell line derived from that has 15-bp deletion EGFR exon 19, under continuous selective pressure low levels without any mutagen, and established subline was able to grow presence 2 μmol/L (designated RPC-9). In line, about half reverse transcription-PCR products mutated also carried an additional mutation (T790M). keeping proposed role T790M abrogating binding EGFR, gefitinib-treated RPC-9 hardly displayed decrease constitutive phosphorylation Akt, or Erk1/2 unlike PC-9 cells. Interestingly, transfection only reversed Thus, balance expression between gefitinib-sensitive gefitinib-resistant govern response lung cancer. [Cancer Res 2007;67(16):7807–14]