Epidermal growth factor receptor double targeting by a tyrosine kinase inhibitor (Iressa) and a monoclonal antibody (Cetuximab). Impact on cell growth and molecular factors.
Epidermal growth factor receptor double targeting by a tyrosine kinase inhibitor (Iressa) and a monoclonal antibody (Cetuximab). Impact on cell growth and molecular factors.
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酪氨酸激酶抑制剂（IRESSA）和单克隆抗体（西妥昔单抗）的表皮生长因子受体双重靶向。对细胞生长和分子因子的影响。
DOI：
10.1038/sj.bjc.6602428
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发表时间：
2005-03-28
影响因子：
8.8
通讯作者：
Milano, G
中科院分区：
文献类型：
--
作者：
Fischel, JL;Formento, P;Milano, G
在肿瘤分子靶向治疗的最新进展中，以表皮生长因子受体（EGFR）为靶点的治疗是目前临床上最有前景和最先进的。鉴于单克隆抗体和酪氨酸激酶抑制剂（TKI）的不同作用模式，研究这两种EGFR靶向方法之间的组合的效果是诱人的。本研究的目的是通过使用两种表皮样人类细胞系CAL 33和CAL 39在实验水平上测试这种组合。由于C225（Cetuximab®）和ZD 1839（Iressa®）分别是抗EGFR药物类别中临床上最先进的药物，因此使用这两种代表性化合物进行实验。C225和ZD 1839的组合在任何细胞系中均具有拮抗作用。细胞凋亡（PARP）和EGFR信号传导（磷酸化p42 -44）的分子变化证实了这些拮抗作用。药物单独导致EGFR水平降低，而它们的组合增加EGFR的细胞表达。这些数据表明，必须谨慎考虑新的和诱人的EGFR靶点治疗策略，包括单克隆抗体和TKI的双重打击。
Among the recent advances in the molecular targeted therapy of cancer, the applications focused on epidermal growth factor receptor (EGFR) are currently the most promising and the most advanced at clinical level. In view of the different modes of action of monoclonal antibodies and tyrosine kinase inhibitors (TKI), it is tempting to examine the effect of a combination between these two EGFR targeting approaches. It was the purpose of the present study to test this combination at experimental level by using two epidermoid human cell lines CAL 33 and CAL 39. As C225 (Cetuximab®) and ZD1839 (Iressa®) are, respectively, the most clinically advanced drugs in the category of anti-EGFR drugs, the experiments were performed using these two representative compounds. The combination of C225 and ZD1839 was antagonistic whatever the cell line considered. These antagonistic effects were corroborated by molecular changes in apoptosis (PARP) and EGFR signalling (phospho-p42–44). Drugs alone led to a diminution in EGFR levels, while their combination increased the cellular expression in EGFR. These data suggest that new and tempting treatment strategies on the EGFR target consisting in a double hit with a monoclonal antibody and a TKI must be considered with caution.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
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