Pao William, Miller Vincent A
Program in Cancer Biology and Genetics and the Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
J Clin Oncol. 2005 Apr 10;23(11):2556-68. doi: 10.1200/JCO.2005.07.799. Epub 2005 Mar 14.
Gefitinib and erlotinib are small molecules that selectively inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. When these drugs were introduced into the clinic, the specific targets affected in human tumors were unknown. In April 2004, two groups reported that mutations in the tyrosine kinase domain of EGFR are strongly associated with gefitinib sensitivity in patients with non-small-cell lung cancer (NSCLC). We subsequently extended these findings and showed that such mutations are also associated with sensitivity to erlotinib. Here, we present current knowledge about EGFR mutations in the context of clinical trials involving gefitinib and erlotinib in NSCLC.
This article reviews the rationale for targeting EGFR, the development of gefitinib and erlotinib, the discovery of EGFR mutations, and subsequent studies to define the incidence, spectrum, and functions of EGFR mutations.
The discovery of EGFR mutations promises to alter the ways in which we consider and treat NSCLC.
This information can guide practitioners and help them inform their patients about EGFR mutations and their impact on the treatment of NSCLC.
吉非替尼和厄洛替尼是选择性抑制表皮生长因子受体（EGFR）酪氨酸激酶活性的小分子。当这些药物引入临床时，人类肿瘤中受影响的具体靶点尚不清楚。2004年4月，两个研究小组报告称，EGFR酪氨酸激酶结构域的突变与非小细胞肺癌（NSCLC）患者对吉非替尼的敏感性密切相关。我们随后扩展了这些发现，并表明此类突变也与对厄洛替尼的敏感性相关。在此，我们在涉及NSCLC患者使用吉非替尼和厄洛替尼的临床试验背景下，介绍关于EGFR突变的现有知识。
本文回顾了靶向EGFR的理论依据、吉非替尼和厄洛替尼的研发、EGFR突变的发现，以及随后确定EGFR突变的发生率、范围和功能的研究。
EGFR突变的发现有望改变我们看待和治疗NSCLC的方式。
这些信息可以指导从业者，并帮助他们告知患者有关EGFR突变及其对NSCLC治疗的影响。
