Epidermal growth factor receptor-mediated signal transduction in the development and therapy of gliomas
Epidermal growth factor receptor-mediated signal transduction in the development and therapy of gliomas
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DOI：
10.1158/1078-0432.ccr-06-0874
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发表时间：
2006-12-15
影响因子：
11.5
通讯作者：
Salgia, Ravi
中科院分区：
文献类型：
--
作者：
Nicholas, M. Kelly;Lukas, Rimas V.;Salgia, Ravi
表皮生长因子受体(EGFR)及其配体在中枢神经系统(CNS)最常见的肿瘤--胶质瘤的生物学中占有重要地位。尽管它们的组织学分类似乎很简单，但这些肿瘤构成了一类不同类型的相关肿瘤。它们与多种影响信号转导、转录因子、细胞凋亡、血管生成和细胞外基质的分子异常有关。在正常情况下，这些相互作用的因素推动中枢神经系统的生长和发育。我们现在认识到，肿瘤在组织学上分为三个不同级别，其背后存在着不同的分子遗传异质性。这一认识导致了直接针对特定分子亚型的新治疗策略。在本文中，我们将综述EGFR及其相关分子通路在正常中枢神经系统发生中的作用及其与神经胶质瘤发生的关系。我们将讨论有效治疗的障碍，因为它们与中枢神经系统的解剖特化有关。我们还将考虑胶质瘤常见的特定EFGR改变如何反映靶向治疗后的结果，所有这些都着眼于将这一理解应用于改善患者的结果。
The epidermal growth factor receptor (EGFR) and its ligands figure prominently in the biology of gliomas the most common tumors of the central nervous system (CNS). Although their histologic classification seems to be straightforward, these tumors constitute a heterogeneous class of related neoplasms. They are associated with a variety of molecular abnormalities affecting signal transduction transcription factors apoptosis angiogenesis and the extracellular matrix. Under normal conditions these same interacting factors drive CNS growth and development. We are now recognizing the diverse molecular genetic heterogeneity that underlies tumors classified histologically into three distinct grades. This recognition is leading to new therapeutic strategies targeted directly at specific molecular subtypes. In this article, we will review the role of EGFR and related molecular pathways in the genesis of the normal CNS and their relationship to glial tumorigenesis. We will discuss barriers to effective treatment as they relate to anatomic specialization of the CNS. We will also consider the ways in which specific EFGR alterations common to glioma reflect outcomes following treatment with targeted therapies all with an eye towards applying this understanding to improved patients outcomes.