Arteaga Carlos L
Department of Medicine, Breast Cancer Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Cancer Cell. 2006 Jun;9(6):421-3. doi: 10.1016/j.ccr.2006.05.014.
Deletions in exon 19 and nucleotide substitutions in exon 21 are the most common mutations of the EGFR (ErbB1) in NSCLC. These mutations endow the receptor with constitutive kinase activity. Most tumors expressing these mutants respond well to EGFR tyrosine kinase inhibitors, suggesting that they are dependent on mutant EGFR signaling. Two groups developed transgenic mice in which expression of these mutants is temporally induced in mouse lung. Mice expressing EGFR mutants develop bronchioloalveolar cancer and lung adenocarcinoma, which are highly sensitive to EGFR inhibitors. These mouse models provide important opportunities for studying the biology of NSCLC and the refinement of anti-EGFR therapies.
外显子19缺失和外显子21中的核苷酸取代是NSCLC中EGFR（ErbB1）最常见的突变。这些突变赋予受体组成型激酶活性。大多数表达这些突变体的肿瘤对EGFR酪氨酸激酶抑制剂反应良好，这表明它们依赖于突变型EGFR信号传导。两个研究小组培育了转基因小鼠，在小鼠肺中可暂时诱导这些突变体的表达。表达EGFR突变体的小鼠会发生细支气管肺泡癌和肺腺癌，这些癌症对EGFR抑制剂高度敏感。这些小鼠模型为研究NSCLC生物学和优化抗EGFR疗法提供了重要机会。
