Epidermal growth factor receptor in glioma

Signal transduction, neuropathology, imaging, and radioresistance1

Research output: Contribution to journalArticle

223 Citations (Scopus)

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

Fingerprint

Epidermal Growth Factor Receptor
Glioma
Signal Transduction
Glioblastoma
erbB-1 Genes
Neoplasms
Neuropathology
Central Nervous System Neoplasms
Gene Amplification
Exons
Radiotherapy
Ligands
Amino Acids

ASJC Scopus subject areas

  • Cancer Research

Cite this

@article{fcc4871183174628af6ef3cf531851a8,
title = "Epidermal growth factor receptor in glioma: Signal transduction, neuropathology, imaging, and radioresistance1",
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.",
author = "Hatanpaa, {Kimmo J.} and Sandeep Burma and Dawen Zhao and Habib, {Amyn A.}",
year = "2010",
month = "9",
doi = "10.1593/neo.10688",
language = "English (US)",
volume = "12",
pages = "675--684",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Epidermal growth factor receptor in glioma

T2 - Signal transduction, neuropathology, imaging, and radioresistance1

AU - Hatanpaa, Kimmo J.

AU - Burma, Sandeep

AU - Zhao, Dawen

AU - Habib, Amyn A.

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77956868654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956868654&partnerID=8YFLogxK

U2 - 10.1593/neo.10688

DO - 10.1593/neo.10688

M3 - Article

VL - 12

SP - 675

EP - 684

JO - Neoplasia (United States)

JF - Neoplasia (United States)

SN - 1522-8002

IS - 9

ER -