Nicholas M Kelly, Lukas Rimas V, Jafri Nazia F, Faoro Leonardo, Salgia Ravi
Department of Neurology, University of Chicago, IL 60637, USA.
Clin Cancer Res. 2006 Dec 15;12(24):7261-70. doi: 10.1158/1078-0432.CCR-06-0874.
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, angiogensesis, 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 EGFR alterations common to glioma reflect outcomes following treatment with targeted therapies, all with an eye towards applying this understanding to improved patient outcomes.
表皮生长因子受体（EGFR）及其配体在胶质瘤生物学中起着重要作用，胶质瘤是中枢神经系统（CNS）最常见的肿瘤。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相关肿瘤的异质性群体。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，这些相同的相互作用因子驱动中枢神经系统的生长和发育。我们现在认识到，组织学上分为三个不同级别的肿瘤背后存在着多样的分子遗传异质性。这种认识正在催生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及相关分子途径在正常中枢神经系统发生中的作用及其与胶质肿瘤发生的关系。我们将讨论与中枢神经系统解剖学特殊性相关的有效治疗障碍。我们还将考虑胶质瘤中常见的特定EGFR改变如何反映靶向治疗后的结果，所有这些都是为了将这种理解应用于改善患者预后。
