Epidermal Growth Factor Receptor as a Predictor of Tumor Response to Preoperative Chemoradiation in Locally Advanced Gastric Carcinoma

Sirák, Igor; Petera, Jiřı́; Hatlová, Jana; Vošmik, Milan; Melichar, Bohuslav; Dvořák, Josef; Zoul, Zdeněk; Tyčová, Věra; Leško, Michal; Hajdúch, Marián

doi:10.1007/s00066-008-1880-9

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…Squamous cell carcinoma in other tumor sites strongly expresses the epidermal growth factor receptor (EGFR), and EGFR overexpression has consistently been demonstrated as negative prognostic factor [18,28]. Only few studies have been performed for anal cancer, but these studies indicate that EGFR is overexpressed in the majority of cases ( Figure 2) [3,15,16,30,31].…”

Section: Role Of Targeted Agentsmentioning

confidence: 99%

Kombinationstherapie des Analkarzinoms. Derzeitige Strategien und zukünftige Entwicklungen

et al. 2010

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Section: Role Of Targeted Agentsmentioning

confidence: 99%

Kombinationstherapie des Analkarzinoms. Derzeitige Strategien und zukünftige Entwicklungen

et al. 2010

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“…A high proportion of human tumor cells is characterized by overexpression of epidermal growth factor receptor (EGFR), a protein that promotes resistance to chemo-and radiotherapy [13,19,31,50,54,58]. EGFR protein can be activated through phosphorylation at specific amino acid residues in response to ligand binding (EGF, tumor necrosis factor-[TGF-]α and amphiregulin) [18,65] as well as after exposure to a variety of unspecific stimuli like ionizing radiation [52], UV radiation [29], hypoxia [45], hyperthermia [17], oxidative stress [28], and transactivation by G-protein-coupled receptors [6].…”

Section: The Outstanding Role Of Egfrmentioning

confidence: 99%

Nuclear EGFR as Novel Therapeutic Target

2009

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Emerging evidence suggests the existence of a new mode of epidermal growth factor receptor (EGFR) signaling in which activated EGFR undergoes nuclear translocation following treatment with ionizing radiation. The authors provide evidence that the nuclear EGFR transport is a stress-specific cellular reaction, which is linked to src-dependent EGFR internalization into caveolae. These flask-shaped pits can fuse with endoplasmic reticulum and the EGFR is sorted into a perinuclear localization. This compartment may serve as a reservoir for nuclear EGFR transport which is regulated by PKCepsilon (protein kinase Cepsilon). Nuclear EGFR is able to induce transcription of genes essential for cell proliferation and cell-cycle regulation. Moreover, nuclear EGFR has physical contact with compounds of the DNA repair machinery and is involved in removal of DNA damage. Anti-EGFR strategies target radiation-associated EGFR nuclear translocation in different manners. EGFR-inhibitory antibodies, i.e., cetuximab (Erbitux((R))), can block nuclear translocation by EGFR immobilization within the cytosol in responder cell lines, whereas tyrosine kinase inhibitors rather target nuclear kinase activity of EGFR linked with cytosolic or nuclear functions. However, both strategies can inhibit DNA repair following irradiation.

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“…tumor response in some cancers and thus represents a therapeutic target for inhibition with small molecules or antibodies [5,8,24,26,33,35].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Caveolin-1 in Lymphoblastoid TK6 Cells Enhances Proliferation After Irradiation with Clinically Relevant Doses

et al. 2010

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Epidermal Growth Factor Receptor as a Predictor of Tumor Response to Preoperative Chemoradiation in Locally Advanced Gastric Carcinoma

Abstract: EGFR may represent a molecular marker predictive for poor response to preoperative chemoradiotherapy in locally advanced gastric carcinoma.

Cited by 9 publications

References 37 publications

Kombinationstherapie des Analkarzinoms. Derzeitige Strategien und zukünftige Entwicklungen

Kombinationstherapie des Analkarzinoms. Derzeitige Strategien und zukünftige Entwicklungen

Nuclear EGFR as Novel Therapeutic Target

Overexpression of Caveolin-1 in Lymphoblastoid TK6 Cells Enhances Proliferation After Irradiation with Clinically Relevant Doses

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