We sought to characterize mRNA and protein content of EV subpopulations released by human glioblastoma (GBM) cells expressing a mutant form of epidermal growth factor receptor (U87<sup>EGFRvIII</sup>) <i>in vitro</i> and <i>in vivo</i> with respect to size, morphology and the presence of tumour cargo.
U87 human GBM cells were treated with the IC50 concentration of various agents used in the treatment of GBM, including alkylating agents (temozolomide, carmustine, lomustine, procarbazine), inhibitor of topoisomerase I (irinotecan), vascular endothelial and epidermal growth factor receptor inhibitors (cediranib and erlotinib, respectively) anti-metabolite (5-fluorouracil), microtubule inhibitor (vincristine), and metabolic agents (dichloroacetate and IDH1 inhibitor ivosidenib).
EGFR-amplified GBMs displayed both a higher number of concrete CNAs and a higher global tumor mutational burden than their no EGFR-amplified counterparts.
Here, we describe recent knowledge on the signaling pathways mediated by EGFR/EGFR variant III (EGFRvIII) with regard to current therapeutic strategies to target EGFR/EGFRvIII amplified glioblastoma.
Genomic analyses reveal that signature genetic lesions in GBM and LGG include copy gain and amplification of chromosome 7, amplification, mutation, and overexpression of receptor tyrosine kinases (RTK) such as EGFR, and activating mutations in components of the PI3K pathway.
We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBMEGFR + cells by modifying STAT3 phosphorylation status.
In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy.
In this study, we developed a cyclic peptide iRGD (CCRGDKGPDC)-conjugated solid lipid nanoparticle (SLN) to deliver small interfering RNAs (siRNAs) against both epidermal growth factor receptor (EGFR) and PD-L1 for combined targeted and immunotherapy against glioblastoma, the most aggressive type of brain tumors.
Hence, we analyzed transcriptome data from glioblastoma cell line SF767 to predict target genes regulated by EGFR isoforms II-IV, but not by EGFR isoform I nor other receptors such as HER2, HER3, or HER4.
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.
Our data identify ALDH levels as a biomarker of GBM cells with high invasive potential, altered oxidative stress, and resistance to EGFR inhibition, and reveal a therapeutic target whose inhibition should limit GBM invasion.
D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma.
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.
To take advantage of these traits, we developed a Drosophila GBM model with constitutively active variants of EGFR and PI3K that effectively recapitulated key aspects of GBM disease.
We demonstrate our method using multimodal high-spectral resolution matrix-assisted laser desorption ionization (MALDI) 9.4 T MSI and 7 T in vivo MRI data, acquired from a patient-derived, xenograft mouse brain model of glioblastoma following administration of the EGFR inhibitor drug of Erlotinib.
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.
Chen and colleagues leverage a <i>Drosophila</i> GBM model to identify a conserved signaling axis downstream of the EGFR and PI3K that involves the death-associated protein kinase (Drak), a cytoplasmic serine/threonine kinase orthologous to the human kinase STK17A.