EGFR and HER2 Expression in advanced Biliary Tract Cancer

Harder, Jan; Waiz, O.; Geißler, Michael; Blum, H. E.; Schmitt‐Gräff, Annette; Opitz, OG

doi:10.1055/s-0028-1089488

Cited by 8 publications

(12 citation statements)

References 24 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunohistochemistry studies have shown that the epidermal growth factor receptor (EGFR) is over expressed in CCA human samples 115,116 . EGFR activation triggers the oncogenic MAPK-ERK signalling pathway in cholangio cytes, making this receptor a potential target for therapy 117 .…”

Section: Growth Factorsmentioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,068

1,139

View full text Add to dashboard Cite

Section: Growth Factorsmentioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,068

1,139

View full text Add to dashboard Cite

“…This pathway is activated by a diverse group of extracellular signals, including growth factor receptors [e.g., EGF receptor (EGFR)]. Expression of EGFR has been validated to be enhanced in tumor samples from 39.2%-46.2% of patients with biliary cancers (6,7). Moreover, activating mutations of KRAS and BRAF can occur in biliary cancers, with reported incidences of 8% to 58% (8) and 0 to 22%, respectively (9), suggesting that activation of the RAF/MAPK signaling pathway may be a key event in a significant proportion of biliary cancers.…”

Section: Introductionmentioning

confidence: 99%

Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer

Knox

Ibrahimov

et al. 2013

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: MEK inhibition has clinical activity against biliary cancers and might therefore be successfully combined with gemcitabine, one of the most active chemotherapy agents for these cancers. As gemcitabine is active in S-phase, and the extracellular signal-regulated kinase (ERK) pathway has a major role driving cellcycle progression, concurrent use of a MEK inhibitor could potentially antagonize the effect of gemcitabine. We therefore tested the sequence dependence of the combination of gemcitabine and the MEK inhibitor AZD6244 using a series of biliary cancer models.Experimental Design: Primary xenografts were established from patients with gallbladder and distal bile duct cancer and grown in severe combined immunodeficient (SCID) mice at the subcutaneous site. Plasma and tumor drug levels and the time course for recovery of ERK signaling and S-phase were measured in tumor-bearing mice treated for 48 hours with AZD6244 and then monitored for 48 hours off treatment. On the basis of these results, two different treatment schedules combining AZD6244 with gemcitabine were tested in four different biliary cancer models.Results: DNA synthesis was suppressed during treatment with AZD6244, and reentry into S-phase was delayed by approximately 48 hours after treatment. Strong schedule dependence was seen in all four biliary cancer models tested, suggesting that combined treatment with AZD6244 plus gemcitabine would be more active in patients with biliary cancer when gemcitabine is given following a 48-hour interruption in AZD6244 dosing, rather than concurrently.Conclusions: The combination of AZD6244 plus gemcitabine is highly schedule dependent, and predicted to be more effective in the clinic using sequential rather than simultaneous dosing protocols.

show abstract

“…(5) Biliary tract cancers express EGFR in 60.7% of cases. (6) The EGFR-overexpressing GBC cases show poorly differentiated histology and decreased survival of 1.5 years in median survival. (7) Amplification and point mutations of the EGFR gene have been reported to be 1% and 15 -26.5%, respectively, in GBC.…”

mentioning

confidence: 99%

Significance of epithelial growth factor in the epithelial–mesenchymal transition of human gallbladder cancer cells

et al. 2012

View full text Add to dashboard Cite

Five gallbladder cancer (GBC) cell lines were examined for morphological changes in collagen gel culture. GBh3 and HUCCT-1 cells formed tubules in response to treatment with epithelial growth factor (EGF) and hepatocyte growth factor (HGF), and showed high levels of expression of E-cadherin (ECD), and low levels of SNAIL, vimentin, transforming growth factor (TGF)-b, and nucleostemin (NS). In contrast, the GBd15 and FU-GBC-1 cell lines treated with EGF and HGF showed a scattering phenotype, and expressed low levels of ECD and high levels of SNAIL, vimentin, TGF-b, and NS. All cell lines expressed the EGF receptor, c-Met, EGF, and TGF-a, but not HGF. Transforming growth factor-b was upregulated by EGF. Knockdown of the EGF receptor abrogated both tubule formation and scattering, whereas KD of TGF-b abrogated only scattering. Knockdown of EGF induced nuclear translocation of b-catenin and Wnt-related NS induction in the scattering cell lines, but not in the tubule-forming cell lines, whereas KD of glycogen synthase kinase-3b in the tubuleforming cell lines resulted in the nuclear translocation of b-catenin and Wnt-related NS induction in response to EGF treatment. These results suggest that EGF enhances epithelial-mesenchymal transformation and acquisition of stemness in GBC cells with a scattering phenotype through the activity of b-catenin. Repression of ECD in scattering GBC cells induced the release of b-catenin from the cell adhesion complexes along the plasma membrane and its translocation to the nucleus to activate Wnt signaling, which upregulated NS. (Cancer Sci 2012; 103: 1165-1171 B iliary tract cancer is the sixth leading cause (5.1%) of cancer death in Japan, with 17 000 BTC patients dying in 2009.(1) Biliary tract cancer shows poor prognosis in spite of aggressive treatment, and the 5-year survival is only 18%.(1) Nodal metastasis is the most significant prognostic factor for GBC. (2)(3)(4) Epithelial growth factor receptor is a key factor in epithelial malignancies, and its activity enhances tumor growth, invasion, and metastasis.(5) Biliary tract cancers express EGFR in 60.7% of cases.(6) The EGFR-overexpressing GBC cases show poorly differentiated histology and decreased survival of 1.5 years in median survival.(7) Amplification and point mutations of the EGFR gene have been reported to be 1% and 15 -26.5%, respectively, in GBC.(8-10) The HGF receptor c-Met is involved in the early carcinogenesis of BTC.(11) c-Met is expressed in 74% of invasive GBC and is associated with invasive depth.(12) Because HGF is secreted from fibroblasts, c-Met activation depends on the cancer-host interaction. (13) Transforming growth factor-b is widely expressed in advanced GBC and is associated with angiogenesis and tumor-associated macrophage infiltration as well as with stromal fibrosis. (14,15) Epidermal growth factor receptor, c-Met, and TGF-b have recently been implicated in the process of EMT. (16)(17)(18)(19) Epithelial-mesenchymal transition comprises a switch in cell differentiation from polarized epithelial ...

show abstract

EGFR and HER2 Expression in advanced Biliary Tract Cancer

Abstract: AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancer (BTC). METHODS

Cited by 8 publications

References 24 publications

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer

Significance of epithelial growth factor in the epithelial–mesenchymal transition of human gallbladder cancer cells

Contact Info

Product

Resources

About