Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
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DOI：
10.1056/nejmoa040938
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发表时间：
2004-05-20
影响因子：
158.5
通讯作者：
Haber, DA
中科院分区：
文献类型：
--
作者：
Lynch, TJ;Bell, DW;Haber, DA
背景：大多数非小细胞肺癌患者对靶向表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂吉非替尼无反应。然而，大约10%的患者具有快速且通常戏剧性的临床反应。潜在的敏感性gefitinib的分子机制是unknown.METHODS：我们寻找突变的EGFR基因在原发性肿瘤的患者与非小细胞肺癌谁有反应gefitinib，那些谁没有反应，和那些谁没有暴露于gefitinib。结果：9例吉非替尼治疗有效的肺癌患者中有8例EGFR基因的酪氨酸激酶结构域发生了体细胞突变，而7例治疗无效的肺癌患者中无一例EGFR基因的酪氨酸激酶结构域发生体细胞突变（P
BACKGROUND:Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown.METHODS:We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells.RESULTS:Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P