Epidermal growth factor receptor in glioma: Signal transduction, neuropathology, imaging, and radioresistance1

Kimmo J. Hatanpaa, Sandeep Burma, Dawen Zhao, Amyn A. Habib

Research output: Contribution to journalReview article

239 Scopus citations

Abstract

Aberrant epidermal growth factor receptor (EGFR) signaling is common in cancer. Increased expression of wild type and mutant EGFR is a widespread feature of diverse types of cancer. EGFR signaling in cancer has been the focus of intense investigation for decades primarily for two reasons. First, aberrant EGFR signaling is likely to play an important role in the pathogenesis of cancer, and therefore, the mechanisms of EGFR-mediated oncogenic signaling are of interest. Second, the EGFR signaling system is an attractive target for therapeutic intervention. EGFR gene amplification and overexpression are a particularly striking feature of glioblastoma (GBM), observed in approximately 40% of tumors. GBM is the most common primarymalignant tumor of the central nervous system in adults. In approximately 50%of tumors with EGFR amplification, a specific EGFR mutant (EGFRvIII, also known as EGFR type III, de2-7, ΔEGFR) can be detected. This mutant is highly oncogenic and is generated from a deletion of exons 2 to 7 of the EGFR gene, which results in an in-frame deletion of 267 amino acids from the extracellular domain of the receptor. EGFRvIII is unable to bind ligand, and it signals constitutively. Although EGFRvIII has the same signaling domain as the wild type receptor, it seems to generate a distinct set of downstream signals that may contribute to an increased tumorigenicity. In this review, wediscuss recent progress in key aspects of EGFR signaling in GBM, focusing on neuropathology, signal transduction, imaging of the EGFR, and the role of the EGFR in mediating resistance to radiation therapy in GBM.

Original languageEnglish (US)
Pages (from-to)675-684
Number of pages10
JournalNeoplasia
Volume12
Issue number9
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Cancer Research

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