Ciardiello Fortunato, De Vita Ferdinando, Orditura Michele, De Placido Sabino, Tortora Giampaolo
Cattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F Magrassi e A Lanzará, Seconda Universitá degli Studi di Napoli, Via S. Pansini 5, 80131 Napoli, Italy.
Expert Opin Emerg Drugs. 2003 Nov;8(2):501-14. doi: 10.1517/14728214.8.2.501.
The epidermal growth factor receptor (EGFR) is a cell membrane receptor that plays a key role in cancer development and progression. Ligand-activated EGFR-dependent signalling is involved in cell proliferation, apoptosis, angiogenesis and metastatic spread. Targeting the EGFR, therefore, represents a promising molecular approach in cancer treatment. Several anti-EGFR agents are in clinical development. Three drugs are currently in Phase II and III development as single agents, or in combination with other anticancer modalities: IMC-225 (cetuximab/Erbitux; ImClone), a chimaeric human-mouse monoclonal IgG(1) antibody, which blocks ligand binding and functional activation of the EGFR; OSI-774 (erlotinib/Tarceva; Genentech/OSI/Roch) and ZD1839 (gefitinib/Iressa; AstraZeneca), two small molecule EGFR-selective inhibitors of tyrosine kinase enzymatic activity, which prevent EGFR autophosphorylation and activation. Iressa is the first EGFR-targeting agent to be registered as an anticancer drug in Japan, in Australia and in the US for the third-line treatment of chemoresistant non-small cell lung cancer (NSCLC) patients. This review will focus on the preclinical background and on the results from the first series of clinical trials with these drugs. Furthermore, continuing clinical trials and a series of open clinical issues for the development of optimal strategies of using EGFR-targeting agents will be discussed.
表皮生长因子受体（EGFR）是一种细胞膜受体，在癌症的发生和发展中起关键作用。配体激活的EGFR依赖性信号传导参与细胞增殖、凋亡、血管生成和转移扩散。因此，靶向EGFR代表了一种有前景的癌症治疗分子方法。几种抗EGFR药物正在进行临床开发。目前有三种药物正在进行II期和III期开发，作为单一药物或与其他抗癌方式联合使用：IMC-225（西妥昔单抗/爱必妥；ImClone），一种人鼠嵌合单克隆IgG(1)抗体，可阻断EGFR的配体结合和功能激活；OSI-774（厄洛替尼/特罗凯；基因泰克/OSI/罗氏）和ZD1839（吉非替尼/易瑞沙；阿斯利康），两种小分子EGFR酪氨酸激酶酶活性选择性抑制剂，可防止EGFR自身磷酸化和激活。易瑞沙是首个在日本、澳大利亚和美国注册为抗癌药物的EGFR靶向药物，用于化疗耐药的非小细胞肺癌（NSCLC）患者的三线治疗。本综述将重点关注这些药物的临床前背景以及首批临床试验的结果。此外，还将讨论正在进行的临床试验以及一系列关于开发使用EGFR靶向药物的最佳策略的未决临床问题。
