Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy: Progression from reversible to irreversible inhibitors
Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy: Progression from reversible to irreversible inhibitors
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DOI：
10.1016/s0163-7258(98)00050-3
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发表时间：
1999-05-01
影响因子：
13.5
通讯作者：
Fry, DW
中科院分区：
文献类型：
--
作者：
Fry, DW
在过去 10 年里，抑制表皮生长因子受体 (EGFR) 酪氨酸激酶家族作为癌症化疗方法的理由不断增强。临床前和临床数据都强烈支持这些受体参与人类癌症的形成和进展，并在癌症患者中建立了受体/配体表达与不良预后之间的高度相关性。在过去的 4 年里，EGFR 酪氨酸激酶抑制剂领域取得了重大进展，新的结构类别已经出现，在效力、特异性以及体外和体内活性方面表现出巨大的改进。最近，该领域取得了进一步的进展，合成了非常特异、不可逆的 EGFR 家族抑制剂，具有独特的药理学特性和卓越的功效。这些现代激酶抑制剂的体内性能已得到改善，一些化合物要么处于临床试验阶段，要么非常接近其开发阶段。这篇综述将简要阐述针对 EGFR 家族进行癌症治疗的理由，然后重点介绍一些正在开发的更有前景的激酶抑制剂。 (C) 1999 爱思唯尔科学公司。
The rationale to inhibit the epidermal growth factor receptor (EGFR) tyrosine kinase family as an approach to cancer chemotherapy has continued to grow stronger over the last 10 years. Both preclinical and clinical data strongly support the involvement of these receptors in the formation and progression of human cancers, as well as establish a high correlation in cancer patients between receptor/ligand expression and poor prognosis. During the past 4 years, significant progress has been made in the area of EGFR tyrosine kinase inhibitors, and new structural classes have emerged that exhibit enormous improvements with regard to potency, specificity, and in vitro and in vivo activity. Very recently, further advancements in this field have been made whereby very specific, irreversible inhibitors of the EGFR family have been synthesized that provide unique pharmacological properties and exceptional efficacy. The in vivo performance of these modern kinase inhibitors has improved to the point where several compounds are either in clinical trials or very near to that point in their development. This review will briefly address the justification for targeting the EGFR family for cancer therapeutics, and then will highlight some of the more promising kinase inhibitors that are in development. (C) 1999 Elsevier Science Inc.