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Epidermal Growth Factor Receptor–Mediated Signal Transduction in the Development and Therapy of Gliomas

Authors' Affiliations: ¹ Department of Neurology and ² Section of Hematology/Oncology, Department of Medicine, University of Chicago and ³ Boston University School of Medicine, Boston, Massachusetts

Requests for reprints: M. Kelly Nicholas, Department of Neurology, University of Chicago, MC 2030, 5841 South Maryland Avenue, Chicago, IL 60637. Phone: 773-834-9026; Fax: 773-702-9076; E-mail: mnichola{at}neurology.bsd.uchicago.edu.

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.

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