Aberrant receptor signaling in human malignant gliomas: mechanisms and therapeutic implications.
Alterations of the epidermal growth factor receptor (EGFR) occur frequently in malignant gliomas through gene amplification or rearrangement, especially in a large fraction of de novo type glioblastomas. The most common of these mutant EGFRs (variously named de2-7 EGFR, deltaEGFR or EGFRvIII) lacks a portion of the extracellular ligand-binding domain. Here, we review the evidence that shows that expression of deltaEGFR bestows in vivo growth advantages to human glioma cells through its constitutively active tyrosine kinase activity. Thus, deltaEGFR may provide a novel therapeutic target for the most aggressive type of glioblastoma.
Nagane
M
M
Ludwig Institute for Cancer Research, San Diego Branch, 3080 CMM-East, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Lin
H
H
Cavenee
W K
WK
Huang
H J
HJ
D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D011799:Quinazolines; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors