EGFR mutation and resistance of non-small-cell lung cancer to gefitinib
EGFR mutation and resistance of non-small-cell lung cancer to gefitinib
复制标题
DOI：
10.1056/nejmoa044238
复制
发表时间：
2005-02-24
影响因子：
158.5
通讯作者：
Halmos, B
中科院分区：
文献类型：
--
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
在对苯胺基喹唑啉EGFR抑制剂有反应的非小细胞肺癌患者中发现了表皮生长因子受体（EGFR）基因突变。尽管对这些抑制剂有显著的反应，但患者最终会复发。耐药机制尚不清楚。在这里，我们报告了一名EGFR突变、吉非替尼敏感的非小细胞肺癌患者的病例，该患者在吉非替尼治疗期间完全缓解两年后复发。复发时活检标本中EGFR基因的DNA序列显示存在第二个点突变，导致EGFR第790位苏氨酸变为甲硫氨酸。结构建模和生化研究表明，这第二个突变导致吉非替尼耐药。
Mutations of the epidermal growth factor receptor ( EGFR) gene have been identified in from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR - mutant, gefitinib-responsive, non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.