Lengyel Ernst, Sawada Kenjiro, Salgia Ravi
University of Chicago, Department of Obstetrics and Gynecology, MC 2050, Section of Gynecologic Oncology, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Curr Mol Med. 2007 Feb;7(1):77-84. doi: 10.2174/156652407779940486.
A subset of tyrosine kinases are activated by mutations which contribute to the malignant transformation, growth, and metastasis of human cancers. Mutations change the expression, conformation and/or stability of tyrosine kinases, often leading to constitutive activation of the signaling pathways the kinases regulate. Given that tyrosine kinases are key members of signaling cascades, mutations have multiple effects on various cellular proteins. This review will focus on four kinases (EGFR, c-Met, c-Kit, and PI3-kinase) known to be mutated in human cancer. It will discuss the effects that these mutations have on the biology of tumors, and how our understanding of the structure and function of kinases and their mutations is currently being used to design targeted treatments.
一部分酪氨酸激酶因突变而被激活，这些突变促成了人类癌症的恶性转化、生长和转移。突变改变了酪氨酸激酶的表达、构象和/或稳定性，常常导致激酶所调控的信号通路发生组成型激活。鉴于酪氨酸激酶是信号级联反应的关键成员，突变会对多种细胞蛋白产生多重影响。本综述将聚焦于已知在人类癌症中发生突变的四种激酶（表皮生长因子受体、c-Met、c-Kit和磷脂酰肌醇-3激酶）。它将讨论这些突变对肿瘤生物学的影响，以及我们目前如何利用对激酶及其突变的结构和功能的理解来设计靶向治疗。
