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>.
The combined hazard ratio (HR) and its 95% confidence intervals (CIs) were used to evaluate the association between EGFR expression and survival in glioma.
Taken together, our results demonstrate that FHL2 interacts with EGFR and EGFRvIII to increase their levels and this promotes glioma growth, representing a novel mechanism that may be therapeutically targetable.
A radiomic signature allowing for the prediction of the EGFR expression level in patients with lower grade glioma was identified, suggesting that using tumour-derived radiological features for predicting genomic information is feasible.
These results suggest that CYP4X1 inhibition in TAMs by CH625 prolongs survival and normalizes tumor vasculature in glioma via CB2 and EGFR-STAT3 axis and may serve as a novel therapeutic strategy for human glioma.
Glioblastomas are discussed as a separate entity due to their high correlation with EGFR mutants and the reported association of the latter with survival and response to treatment in this glioma subgroup.
However inhibition of EGFR did enhance the chemo- and radio-sensitivity of both canine and human glioma CSCs, enabling this resistant, tumourigenic population of cells to be effectively targeted by conventional therapies.
In conclusion, different SNPs in EGFR gene might have different impacts on the risk of glioma in various ethnicities, which offers new insights into the treatment with a target-oriented approach.
ABY-029, a synthetic Affibody peptide, Z03115-Cys, labeled with a near-infrared fluorophore, IRDye® 800CW, targeting epidermal growth factor receptor (EGFR) has been produced under good manufacturing practices for a US Food and Drug Administration-approved first-in-use human study during surgical resection of glioma, as well as other tumors.
Fluorescence-guided surgery is promising for its ability to enhance contrast through exogenous fluorophores; however, the specificity and sensitivity of the underlying contrast mechanism and tumor delivery and uptake vary widely across approved and emerging agents.<b>Experimental Design:</b> Rats with orthotopic F98 wild-type and F98 EGFR-positive (EGFR<sup>+</sup>) gliomas received <i>in vivo</i> administration of IRDye680RD, 5-aminioleuvulinic acid, and ABY-029-markers of perfusion, protoporphyrin metabolism, and EGFR expression, respectively.
Its efficacy as a single agent or in combination with TMZ was assessed <i>in vitro</i> and <i>in vivo</i> using zebrafish and patient-derived GSC xenograft mouse glioma models.<b>Results:</b> Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs.
When we excluded the studies with small sample size (case number < 1000), a significant association between EGFRrs2252586 mutation and glioma susceptibility remained (OR=1.16; 95%CI, 1.09-1.22; P<0.00001).
The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM).
Indeed, as glioma is driven by aberrant signaling of growth factor receptors, particularly the EGFR, iPA, alone or in association with EGFR targeted therapies, might be a promising therapeutic tool to achieve a potent anti-tumoral effect.
Our results imply that GOLPH3 promotes glioma cell proliferation via inhibiting Rab5-mediated endocytosis and degradation of EGFR, thereby activating the phosphatidylinositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway.