Egfr
Sort
Pubmeds
(6,902)
Gene
Egfr -Epidermal growth factor receptor
Related with
Pubmeds(6932)
Pathways(40)
Drugs or chemicals(24)
Diseases(11)
Clinical trials(16)
Pubmed
To re-treat or not with gefitinib/erlotinib: This is the question for tyrosine kinase inhibitor-responsive lung cancers that progress.
Journal: Lung cancer (Amsterdam, Netherlands)
October/17/2007
Authors
Related with
Citations(1)
Genes(1)
Drugs or chemicals(5)
Diseases(3)
Organisms(1)
Processes(2)
Authors(1)
Pubmed
FM807, a curcumin analogue, shows potent antitumor effects in nasopharyngeal carcinoma cells by heat shock protein 90 inhibition.
Journal: Oncotarget
August/27/2017
Description

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy usually associated with overexpression of both epidermal growth factor receptor (EGFR) and β-catenin. FM807 is a novel curcumin analogue with antitumor activity against both poorly and well-differentiated NPC cell lines as well as good selectivity for tumor cells. FM807 actions were shown to include inhibition of cell growth, induction of necrotic/late apoptotic cell death, and G1 arrest in NPC cells. Crucially, it exhibited potent antitumor effects both in vitro and in vivo. Binding of FM807 to the N-terminus of Hsp90 disrupted Hsp90/client complexes, resulting in degradation of the Hsp90 client protein EGFR and inhibition of the downstream Raf/MEK/ERK and PI3K/AKT pathway. FM807 also depleted levels of the intranuclear transcription factors β-catenin, Cyclin D1 and c-Myc levels by inhibiting Hsp90 chaperoned nuclear transport. In conjunction with its low toxicity in NPC xenograft mice, these results provide a sound preclinical basis for further development of FM807 as a novel therapeutic agent in the treatment of NPC.

Read more
Authors
; ; ; ; ;
Related with
Citations(1)
References(51)
Genes(2)
Drugs or chemicals(6)
Diseases(1)
Organisms(4)
Processes(6)
Anatomy(1)
Affiliates(1)
Authors(6)
Pubmed
Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment.
Journal: Annals of oncology : official journal of the European Society for Medical Oncology
September/1/2017
Description

UNASSIGNED

The efficacy of programmed death-1 blockade in epidermal growth factor receptor gene (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR.

UNASSIGNED

We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) density in tumor specimens obtained after acquisition of EGFR-TKI resistance were determined by immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations. The relation of T790M status to PD-L1 expression or TIL density was also examined in an independent cohort of 60 patients (cohort B).

UNASSIGNED

In cohort A, median progression-free survival (PFS) was 2.1 and 1.3 months for T790M-negative and T790M-positive patients, respectively (P = 0.099; hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was 2.1 and 1.3 months for patients with a PD-L1 expression level of ≥1% or <1%, respectively (P = 0.084; hazard ratio of 0.37, 95% confidence interval of 0.10-1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff values of ≥10% and ≥50%. The proportion of tumors with a PD-L1 level of ≥10% or ≥50% was higher among T790M-negative patients than among T790M-positive patients of both cohorts A and B. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden.

UNASSIGNED

T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level, than are T790M-positive patients.

Read more
Authors
; ; ; ; ; +16 authors
Related with
Citations(2)
Genes(1)
Affiliates(3)
Authors(22)
Pubmed
Co-targeting of EGF receptor and neuropilin-1 overcomes cetuximab resistance in pancreatic ductal adenocarcinoma with integrin β1-driven Src-Akt bypass signaling.
Journal: Oncogene
September/6/2017
Description

Pancreatic ductal adenocarcinoma (PDAC) cells usually overexpress the epidermal growth factor receptor (EGFR); however, most are resistant to the anti-EGFR monoclonal antibody, cetuximab. In this study, we report that the molecular mechanism of resistance to cetuximab in PDAC cells is mediated by the overexpression of active integrin β1 with downstream Src-Akt activation; this triggers an EGFR ligand-independent proliferation signaling, bypassing EGFR-blocking effect. Knockdown of integrin β1 or inhibition of Src or Akt sensitized cetuximab-resistant (CtxR) PDAC cells to cetuximab. We found that neuropilin-1 (NRP1) physically interacts with active integrin β1, but not inactive one, on the cell surface. To inhibit active integrin β1-driven signaling by targeting NRP1, while suppressing EGFR signaling, we generated an EGFR and NRP1 dual targeting antibody, Ctx-TPP11, by genetic fusion of the NRP1-targeting peptide, TPP11, to the C terminus of the cetuximab heavy chain (Ctx-TPP11). We demonstrate that Ctx-TPP11 efficiently inhibited the growth of CtxR PDAC cells, in vitro and in vivo. The sensitization mechanism involved downregulating active integrin β1 levels through NRP1-coupled internalization mediated by the TPP11 moiety, leading to the inhibition of active integrin β1-driven bypass signaling. Our findings identify aberrant active integrin β1-driven Src-Akt hyperactivation as a primary resistance mechanism to cetuximab in PDAC cells and offer an effective therapeutic strategy to overcome this resistance using an EGFR and NRP1 dual targeting antibody.

Read more
Authors
; ; ; ;
Related with
Citations(2)
Genes(2)
Drugs or chemicals(6)
Diseases(2)
Organisms(3)
Processes(2)
Anatomy(1)
Affiliates(2)
Authors(5)
Pubmed
Argos mutants define an affinity threshold for spitz inhibition in vivo.
Journal: The Journal of biological chemistry
November/26/2006
Description

Argos, a secreted antagonist of Drosophila epidermal growth factor receptor (dEGFR) signaling, acts by sequestering the activating ligand Spitz. To understand how different domains in Argos contribute to efficient Spitz sequestration, we performed a genetic screen aimed at uncovering modifiers of an Argos misexpression phenotype in the developing eye. We identified a series of suppressors mapping to the Argos transgene that affect its activity in multiple developmental contexts. These point mutations map to both the N- and C-terminal cysteine-rich regions, implicating both domains in Argos function. We show by surface plasmon resonance that these Argos mutants are deficient in their ability to bind Spitz in vitro. Our data indicate that a mere approximately 2-fold decrease in K(D) is sufficient to compromise Argos activity in vivo. This effect could be recapitulated in a cell-based assay, where a higher molar concentration of mutant Argos was needed to inhibit Spitz-dependent dEGFR phosphorylation. In contrast, a approximately 37-fold decrease in the binding constant nearly abolishes Argos activity in vivo and in cellular assays. In agreement with previously reported computational studies, our results define an affinity threshold for optimal Argos inhibition of dEGFR signaling during development.

Read more
Authors
; ; ; ;
Related with
Citations(2)
Grants(6)
Genes(4)
Drugs or chemicals(6)
Organisms(2)
Processes(5)
Anatomy(1)
Affiliates(1)
Authors(5)
Pubmed
Overexpression of transglutaminase in the Drosophila wing imaginal disc induced an extra wing crossvein phenotype.
Journal: Bioscience, biotechnology, and biochemistry
March/27/2011
Description

To determine the roles of Drosophila transglutaminase-A (dTG-A), we examined a phenotype induced through ectopic expression of dTG-A. Overexpression of dTG-A in the wing imaginal disc induced an extra wing crossvein phenotype. This phenotype was suppressed by crossing with epidermal growth factor receptor (Egfr) signaling pathway mutant flies. These results indicate that this phenotype, induced by dTG-A, is related to enhancement of the Egfr signaling pathway.

Read more
Authors
; ; ; ; ; ;
Related with
Citations(2)
Genes(3)
Organisms(2)
Processes(2)
Anatomy(1)
Affiliates(1)
Authors(7)
Pubmed
Expression and mutation analysis of EGFR, c-KIT, and β-catenin in pulmonary blastoma.
Journal: Journal of clinical pathology
August/16/2011
Description

BACKGROUND

Pulmonary blastoma (PB) is a rare malignant lung tumour with an immature mesenchymal and epithelial component resembling fetal lung. In order to define potential therapeutic targets in PB, the authors analysed the status and possible role of EGFR, HER2 and c-KIT in the pathogenesis of this tumour type, and the diagnostic value of β-catenin mutation analysis in PB.

METHODS

5 PBs were analysed for EGFR, HER2, c-KIT, and β-catenin expression, as well as for mutations in EGFR, c-KIT, k-ras and the β-catenin gene (CTNNB1).

RESULTS

EGFR expression was observed in all PBs. An EGFR mutation was found in one of the tumours. No overexpression of c-KIT or HER2 was seen. No mutations were found in k-ras or c-KIT. 3 of 5 PBs displayed CTNNB1 mutations. Nuclear translocation of β-catenin was seen in 2 of these tumours.

CONCLUSIONS

Detection of EGFR expression and mutation in PB suggest EGFR inhibition as a potential therapeutic option in the treatment of advanced PB. Moreover, the data confirm a crucial role of CTNNB1 mutations in the pathogenesis of PB, and indicate that CTNNB1 gene sequencing may be a useful in distinguishing PB from other types of lung cancer.

Read more
Authors
; ; ; ; ; +2 authors
Related with
Citations(2)
Genes(1)
Drugs or chemicals(6)
Diseases(2)
Organisms(1)
Processes(2)
Affiliates(1)
Authors(8)
Pubmed
Dual inhibition of both the epidermal growth factor receptor and erbB2 effectively inhibits the promotion of skin tumors during two-stage carcinogenesis.
Journal: Cancer prevention research (Philadelphia, Pa.)
December/5/2010
Description

The erbB family of receptor tyrosine kinases are known to play important roles in normal epithelial development and epithelial neoplasia. Considerable evidence also suggests that signaling through the epidermal growth factor receptor (EGFR) plays an important role in multistage skin carcinogenesis in mice; however, less is known about the role of erbB2. In this study, to further examine the role of both erbB2 and EGFR in epithelial carcinogenesis, we examined the effect of a dual erbB2/EGFR tyrosine kinase inhibitor, GW2974, given in the diet on skin tumor promotion during two-stage carcinogenesis in wild-type and BK5.erbB2 mice. In BK5.erbB2 mice, erbB2 is overexpressed in the basal layer of epidermis and leads to heightened sensitivity to skin tumor development. GW2974 effectively inhibited skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in wild-type and BK5.erbB2 mice, although a more marked effect was seen in BK5.erbB2 mice. In addition, this inhibitory effect was reversible when GW2974 treatment was withdrawn. GW2974 inhibited 12-O-tetradecanoylphorbol-13-acetate-induced epidermal hyperproliferation, which correlated with reduced activation of both the EGFR and erbB2. These results support the hypothesis that both the EGFR and erbB2 play an important role in the development of skin tumors during two-stage skin carcinogenesis, especially during the tumor promotion stage. Furthermore, the marked sensitivity of BK5.erbB2 mice to the inhibitory effects of GW2974 during tumor promotion suggest greater efficacy for this compound when erbB2 is overexpressed or amplified as an early event in the carcinogenic process.

Read more
Authors
; ; ; ; ; +3 authors
Related with
Citations(2)
References(61)
Grants(8)
Genes(2)
Drugs or chemicals(5)
Diseases(4)
Organisms(3)
Processes(2)
Anatomy(1)
Authors(9)
Pubmed
Expression of p16 protein and epidermal growth factor receptor in patients with adenocarcinoma of the uterine cervix: an immunohistochemical analysis.
Journal: Archives of gynecology and obstetrics
June/23/2011
Description

OBJECTIVE

The present study assessed the expression of p16 and epidermal growth factor receptor (EGFR) in patients with adenocarcinoma of the uterine cervix to determine their influence on prognosis and to evaluate a possible association between their expression and various clinicopathologic parameters.

METHODS

p16 and EGFR expression was investigated by immunohistochemistry from paraffin-embedded tissue in 39 patients with adenocarcinoma of the uterine cervix. The immunohistochemical findings were correlated with different clinicopathologic parameters of the patients.

RESULTS

p16 was expressed in 56% of the patients. A trend towards increased lymph vascular space invasion was observed in p16 positive tumors (p = 0.06). There was no statistically significant association between p16 expression and clinical stage, age, histology, tumor size, tumor grade, lymph node status and recurrence disease (p > 0.05). p16 expression did influence neither disease-free nor overall survival (p > 0.05). EGFR was expressed in 44% of the patients. There was no statistically significant correlation between EGFR expression and clinical stage, age, histology, tumor size, tumor grade, lymph vascular space invasion, lymph node status and recurrence disease (p > 0.05). EGFR expression did influence neither disease-free nor overall survival (p > 0.05).

CONCLUSIONS

p16 and EGFR are frequently expressed in adenocarcinoma of the uterine cervix. Our study observed a trend towards increased lymph vascular space invasion in p16 positive tumors. Otherwise, the expression of the investigated parameters did not correlate with any clinicopathologic parameters and had no influence on overall and disease-free survival. So far, the investigation of p16 and EGFR is of limited use to assess patients' prognosis and guide clinical management.

Read more
Authors
; ; ; ; ;
Related with
Citations(3)
Genes(2)
Drugs or chemicals(4)
Diseases(2)
Organisms(1)
Anatomy(1)
Authors(6)
Pubmed
Correlation of epidermal growth factor receptor mutation, immunohistochemistry, and fluorescence in situ hybridization in esophageal squamous cell carcinoma.
Journal: Journal of the Medical Association of Thailand = Chotmaihet thangphaet
November/30/2009
Description

BACKGROUND

The epidermal growth factor receptor (EGFR) has become a promising target for novel anticancer therapy Evaluation of its biological profiles including gene mutation, amplification, and protein expression in esophageal squamous cell carcinoma (ESCC) is essential to establish the EGFR molecular feature(s) suitable to select patients in anti-EGFR therapy.

METHODS

The subjects' specimens of ESCC at Songklanagarind Hospital were obtained and investigated for EGFR protein expression and gene amplification. Polymerase chain reaction (PCR) was performed to amplify the EGFR DNA product. The mutational status of EGFR exons 19 and 21 was analyzed using direct sequencing. The entire biological profiles of the EGFR were then correlated.

RESULTS

There were 48 eligible ESCC specimens. No somatic mutation in the tyrosine kinase domain of EGFR was detected A high level of EGFR protein was exhibited in 22 patients (46%). Twenty-three patients (48%) had shown a high gene copy numbers. However, no direct correlation between EGFR protein and gene status was observed.

CONCLUSIONS

EGFR mutations in the tyrosine kinase domain of exons 19 and 21 were absent in ESCC, whereas, protein overexpression and gene amplification was prevalent. Therefore, selection of ESCC patients for studies with anti-EGFR agents based on protein expression or gene copy number, not gene mutation, is rational.

Read more
Authors
; ; ; ;
Related with
Citations(3)
Genes(1)
Drugs or chemicals(1)
Diseases(2)
Organisms(1)
Processes(2)
Affiliates(1)
Authors(5)
load more...