The sensitivity of lung cancer cell lines to the EGFR-selective tyrosine kinase inhibitor ZD1839 ('Iressa") is not related to the expression of EGFR or HER-2 or to K-ras gene status
The sensitivity of lung cancer cell lines to the EGFR-selective tyrosine kinase inhibitor ZD1839 ('Iressa") is not related to the expression of EGFR or HER-2 or to K-ras gene status
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DOI：
10.1016/s0169-5002(03)00278-2
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发表时间：
2003-10-01
期刊：
影响因子：
5.3
通讯作者：
Hida, T
中科院分区：
文献类型：
--
作者：
Suzuki, T;Nakagawa, T;Hida, T
ZD 1839（“易瑞沙”）是一种表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），可抑制EGFR信号传导。新出现的证据表明，ZD 1839在肺癌中具有临床潜力，但对可能决定对ZD 1839敏感性的肺癌分子特征知之甚少。我们检测了一组19个肺癌细胞系，以研究ZD 1839敏感性与组织学类型、表达水平和EGFR和K-ras基因状态的组成性磷酸化之间的可能关联。我们的结果表明，EGFR的表达水平和组成性激活状态似乎都不能预测对ZD 1839的敏感性。此外，ZD 1839敏感性与人表皮生长因子受体2（HER-2）（该酪氨酸激酶受体家族的另一个成员）的表达无关，也与EGFR和HER-2的共表达无关。最后，未发现K-ras基因（EGFR转导信号的重要下游介质）激活突变的存在与对ZD 1839的相对耐药性之间存在相关性。这些发现保证了未来的研究，以阐明ZD 1839如何抑制肺癌细胞生长，并找到一个有用的标志物，用于预测对这种新型和有前途的肺癌治疗药物的敏感性。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
ZD1839 ('Iressa') is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that inhibits EGFR signaling. Emerging evidence indicates that ZD1839 has clinical potential in lung cancer, but very little is known about the molecular characteristics of lung cancers that may determine sensitivity to ZD1839. We examined a panel of 19 lung cancer cell lines to investigate possible association between ZD1839 sensitivity and histological type, expression level and constitutive phosphorylation of EGFR and K-ras gene status. Our results indicate that neither expression level nor constitutive activation status of EGFR seems to predict sensitivity to ZD1839. In addition, ZD1839 sensitivity was not associated with expression of human epidermal growth factor receptor-2 (HER-2), another member of this tyrosine kinase receptor family nor with co-expression of EGFR and HER-2. Finally, no correlation was found between the presence of activating mutations of the K-ras gene, an important downstream mediator of the EGFR-transduced signals and the relative resistance to ZD1839. These findings warrant future study to clarify how ZD1839 inhibits lung cancer cell growth and to find a useful marker for prediction of sensitivity to this novel and promising agent for the treatment of lung cancers. (C) 2003 Elsevier Ireland Ltd. All rights reserved.