Amplification of epidermal growth factor receptor (EGFR) and active mutant EGFRvIII occurs frequently in glioblastoma (GBM) and contributes to chemo/radio-resistance in various cancers, especially in GBM.
Importantly, MYST1 expression was lowly expressed in mesenchymal subtype of GBM and was positively correlated with EGFR expression in a cohort from The Cancer Genome Atlas.
Four genes that were commonly altered in both primary and recurrent GBM were more prevalent in our cohort than reported in COSMIC: CDKN2A (86% vs. 53%) and CDKN2B (86% vs. 54%) deletions, EGFR activating mutation (52% vs. 10%) or amplification (81% vs. 45%), and TERT mutation (95% vs. 51%).
For glioblastoma (GBM), the epidermal growth factor receptor (EGFR) gene is the most frequently mutated oncogenic driver and has therefore been considered an attractive target for therapy.
The IC<sub>50</sub> values ranged from 17.34 µg/mL (towards U87MG.ΔEGFRglioblastoma cells) to 40.68 µg/mL (against CCRF-CEM leukemia cells) for FTB, from 16.78 µg/mL (towards U87.
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.
As therapeutic decisions are increasingly guided by biomarkers, and EGFR abnormalities are common in GBM, thus representing a potential therapeutic target, we systematically evaluated methods of assessing <i>EGFR</i> amplification by multiple assays.
The prognosis value of the risk signature was superior than known clinicopathological features in 1p/19q non-codel gliomas and was also highly associated with the following features: loss of CDKN2A/B copy number in mutant-IDH-astrocytoma; telomerase reverse transcriptase (TERT) promoter mutation, combined chromosome 7 gain/chromosome 10 loss and epidermal growth factor receptor amplification in wild-type-IDH-astrocytoma; classical and mesenchymal subtypes in glioblastoma.
Glioblastomas (GBs) frequently display activation of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR). mTOR exists as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2).
D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma.
In addition, we found that specific FOXO3a activation recapitulated the molecular effects of EGFR inhibition, and that the FOXO3a activator trifluoperazine, a FDA-approved antipsychotic agent, reduced GBM cell growth.
The IC<sub>50</sub> values of the compounds against carcinoma cells varied from 16.90 µM (in resistant U87MG.ΔEGFRglioblastoma cells) to 48.67 µM (against HepG2 hepatocarcinoma cells) for 1, from 7.85 µM (in U87MG.ΔEGFR cells) to 14.44 µM (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 µM (towards U87MG.ΔEGFRcells) to 7.76 µM (against MDA-MB231/BCRP cells) for 4, and from 0.07 µM (against MDA-MB231 cells) to 2.15 µM (against HepG2 cells) for doxorubicin.
EGFR-amplified diffuse gliomas are "glioblastoma-like" in their behavior and may represent undersampled glioblastomas, or subsets of IDH-wildtype diffuse gliomas with inherently aggressive biology.
These data provide early evidence that combining HDAC and EGFR inhibition may be an effective strategy to reduce GBM growth, through a mechanism possibly involving STAT3.
High levels of NO66 in glioma and glioblastoma tissues predict poor patient prognosis, and NO66 is required for EGFR expression and glioblastoma cell proliferation.
Abnormal activation of epidermal growth factor receptors (EGFRs) due to amplification, mutation, or both of the <i>EGFR</i> gene is common in glioblastomas.
Neutralizing antibody against BTC abrogated activation of both EGFR and NF-ᴋB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in glioblastoma cells.
We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBMEGFR + cells by modifying STAT3 phosphorylation status.