Growth suppression of intracranial xenografted glioblastomas overexpressing mutant epidermal growth factor receptors by systemic administration of monoclonal antibody (mAb) 806, a novel monoclonal antibody directed to the receptor.
Hemizygous or homozygous deletion of the chromosomal region containing the p16INK4a gene is associated with amplification of the EGF receptor gene in glioblastomas.
These findings suggest that a single nucleotide polymorphism in EGF may play a role in the formation of glioblastomas, is a useful and powerful prognostic marker for these patients, and may be a target for tumor therapy.
The EGF receptor (EGFR) is amplified and mutated in glioblastoma, in which its common mutation (ΔEGFR, also called EGFRvIII) has a variety of activities that promote growth and inhibit death, thereby conferring a strong tumor-enhancing effect.
We further compared EGF+61 G/A polymorphism in patients with glioblastoma and Grade I-III glioma accordingly, the stronger association between the EGF +61 G/A polymorphism and the malignancy of glioma was found.
Particularly salient are the following: (1) gene amplification is related to increasing grade of human glioma malignancy and occurs in approximately 40% of the most common and most malignant variety of glioma, glioblastoma multiforme (GBM), (2) by far the most commonly amplified gene in glioblastomas is the epidermal growth factor receptor (EGFR) gene, which is amplified in about one third of GBMs, (3) a small percentage of GBMs amplify N-myc or the novel sequence gli, (4) the EGFR gene is rearranged in at least half of gliomas in which it is amplified, and (5) EGFR gene rearrangement results in external domain deletions that yield truncated EGF receptors.
Here, we show the first example of this alternate mechanism in brain tumors by showing that EGF receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing platelet-derived growth factor receptor β (PDGFRβ).
EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor and has been detected in a large percentage of patients with glioblastoma multiforme but not in normal brain.
Primary (de novo) glioblastomas develop in older patients and are characterized by epidermal growth factor (EGF) receptor amplification/overexpression, p16 deletion, and PTEN mutations, whereas secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma develop in younger patients and frequently contain p53 mutations.
Diphtheria toxin-epidermal growth factor fusion protein and Pseudomonas exotoxin-interleukin 13 fusion protein exert synergistic toxicity against human glioblastoma multiforme cells.
According to the prevailing model, NHE9 overexpression leads to an increase in plasma membrane density of epidermal growth factor receptors (EGFRs) which consequently enhances GBM cell proliferation and migration.
Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
Here we developed a purification strategy to directly isolate EGFR<sup>+/-</sup> populations from human germinal matrix (GM) and adult subventricular zone autopsy tissues, and from de novo glioblastoma (GBM) resections, enriching for cells capable of binding EGF ligand (<sup>LB</sup>EGFR<sup>+</sup>), and uniquely compared their functional and molecular properties.