Specifically, targeting cellular pathways frequently altered in glioblastoma, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), the p53 and the retinoblastoma (RB) pathways, or epidermal growth factor receptor (EGFR) gene amplification or mutation, have failed to improve outcome, likely because of redundant compensatory mechanisms, insufficient target coverage related in part to the blood brain barrier, or poor tolerability and safety.
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.
To evaluate the frequency of MGMT methylation status in a single institute series of 134 GBMs and correlate it with clinical (age, sex, location, survival) and other molecular parameters [such as p53 expression, alpha thalassemia/mental retardation syndrome X-linked (ATRX) expression, isocitrate dehydrogenase (IDH) 1R132H mutation, and epidermal growth factor receptor (EGFR) gene amplification].
EGFRvIII-specific CAR-T cells were unable to completely treat tumors with heterogenous EGFRvIII expression, leading to outgrowth of EGFRvIII-negative, EGFR-positive glioblastoma.
Macropinocytosis may be notably triggered by epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR), two well-known markers for glioblastoma aggressiveness.
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.
WITHDRAWAL: Significant effect of anti-tyrosine kinase inhibitor (Gefitinib) on overall survival of the Glioblastoma (GBM) patients in the backdrop of mutational status of EGFR and PTEN genes.
Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib.
These findings substantiate a critical role for the TROY-EGFR complex in regulation of glioblastoma cell invasion.<b>Implications:</b> The TROY-EGFR signaling complex emerges as a potential therapeutic target to inhibit glioblastoma cell invasion.<i></i>.
Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM), generated by deletion of exons 2 to 7 of EGFR.
These results are consistent with and corroborate our previous findings demonstrating that targeting these two parallel pathways with c-Met and EGFR inhibitor therapy provides substantial anti-tumor activity in glioblastoma models.
Overexpression of EGFR was found to be an indicator of poor prognosis in overall survival in glioma patients (HR =1.72, 95% CI 1.32-2.25, <i>P</i>=0.000, random effect) and glioblastoma multiforme patients (HR =1.57, 95% CI 1.15-2.14, <i>P</i>=0.004, random effect).
Together, our results suggested that Cx43 acts as an inhibitory regulator of the activation of growth factor receptor downstream signaling pathways, indicating the potential of Cx43 as a marker for predicting the efficacy of EGFR inhibitor treatments for GBM.
The findings of this study indicate a highly invasive phenotype associated with the EGFR<sup>A289V</sup> mutation in glioblastoma, postulating EGFR<sup>A289V</sup> as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism.
Our study identifies TRIM59 as a new regulator of oncogenic EGFR/STAT3 signaling and as a potential therapeutic target for GBM patients with EGFR activation.<b>Significance:</b> These findings identify a novel component of the EGFR/STAT3 signaling axis in the regulation of glioma tumorigenesis.<i></i>.
It was previously demonstrated that LRIG2 positively regulates epidermal growth factor receptor (EGFR) signaling, the most common aberrant receptor tyrosine kinase (RTK) signaling in glioblastoma multiforme (GBM), which promotes GBM growth.
Hyper-activation of epidermal growth factor receptor (EGFR) signaling is characteristic of several different classes of human cancers, including a subset of glioblastoma and medulloblastoma.