Arteaga Carlos L
Departments of Medicine and Cancer Biology and the Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-6307, USA.
Semin Oncol. 2002 Oct;29(5 Suppl 14):3-9. doi: 10.1053/sonc.2002.35642.
The ability of the epidermal growth factor receptor (EGFR) to transform epithelial cells, the overexpression of EGFR and its ligands in several human carcinomas, and the causal association of the receptor network with accelerated tumor progression provided a rationale for targeting this signaling system with tumor-selective strategies. Two of these antireceptor approaches, both based on the known structure/function of the EGFR, will be discussed. The first strategy involved the development of humanized monoclonal antibodies against the nonconserved receptor's extracellular domain. These antibodies block ligand binding and can induce receptor downregulation. The second approach was the generation of adenosine triphosphate-mimetics that compete with adenosine triphosphate for binding to the receptor's kinase pocket and disable the ability of the EGFR to transduce intracellular signals. Early clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, alter the natural history of EGFR-expressing cancers with little toxicity to the tumor-bearing host.
表皮生长因子受体（EGFR）转化上皮细胞的能力、EGFR及其配体在几种人类癌症中的过表达，以及受体网络与肿瘤进展加速之间的因果关联，为采用肿瘤选择性策略靶向这一信号系统提供了理论依据。本文将讨论基于EGFR已知结构/功能的两种抗受体方法。第一种策略是开发针对非保守受体胞外结构域的人源化单克隆抗体。这些抗体可阻断配体结合并能诱导受体下调。第二种方法是生成三磷酸腺苷模拟物，其与三磷酸腺苷竞争结合受体的激酶结构域，从而使EGFR丧失转导细胞内信号的能力。早期临床研究已表明，这两种方法单独使用或与标准抗癌疗法联合使用，均可改变EGFR表达型癌症的自然病程，且对荷瘤宿主的毒性很小。
