Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer.

Dassonville, O.; Formento, J. L.; Francoual, M; Ramaioli, A.; Santini, J.; Schneider, M.; Démard, F; Milano, G.

doi:10.1200/jco.1993.11.10.1873

Cited by 372 publications

(219 citation statements)

References 19 publications

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“…The study focused on human head and neck cancer cell lines as neoangiogenesis plays a critical role in the development and evolution of tumours arising from the upper aero-digestive tract (Nakaya et al, 2005;Shang and Lir, 2005). Head and neck cancer is also known to express high levels of EGFR with a strong prognostic value, and the 'drugable' relevance of this growth factor has been reported by others Grandis, 2003, 2004) and us (Dassonville et al, 1993;Etienne et al, 1999;Pivot et al, 2005).…”

Section: Discussionmentioning

confidence: 97%

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Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

et al. 2006

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Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising agent, with gefitinib and irradiation on the growth of six head and neck human cancer cell lines xenografted in nude mice and to study predictive and molecular factors responsible for antitumour effects. CAL33-and Hep-2-grafted cell lines were the most sensitive to ZD6126 treatment, with VEGF levels significantly higher (P ¼ 0.0336) in these tumour xenografts compared to Detroit 562-and CAL27-grafted cell lines with relatively low VEGF levels that were not sensitive to ZD6126. In contrast, neither IL8 levels nor EGFR expression was linked to the antitumour effects of ZD6126. ZD6126 in combination with gefitinib resulted in a synergistic cytotoxic interaction with greater antitumour effects than gefitinib alone. The synergistic interaction between ZD6126 and gefitinib was corroborated by a significant decrease in CD31 labelling. The present study may serve for future innovative clinical applications, as it suggests that VEGF tumour levels are possible predictors for ZD6126 antitumour efficacy. It also supports the notion of antitumour supra-additivity when combining gefitinib and ZD6126, and identifies neoangiogenesis as the main determinant of this synergistic combination.

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Section: Discussionmentioning

confidence: 97%

“…These cell lines exhibit variable EGFR levels (ligand-binding assay; Dassonville et al, 1993), doubling time, in vitro sensitivities to gefitinib or RT and p53 status, as summarised in Table 1.…”

Section: Cell Linesmentioning

confidence: 99%

Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

et al. 2006

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“…This cell line exhibits high EGFR levels (33 7947624 fmol mg À1 protein high-affinity sites determined by ligand binding assay; Dassonville et al, 1993) and produces VEGF (C Onesto, CNRS-UMR6543, personal communication).…”

Section: Cell Linesmentioning

confidence: 99%

Dual inhibition of EGFR and VEGFR pathways in combination with irradiation: antitumour supra-additive effects on human head and neck cancer xenografts

Bozec

Formento

Lassalle³

et al. 2007

Br J Cancer

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The aim of this study was to investigate the effects of combining antiangiogenic treatment, epidermal growth factor receptor (EGFR) targeting and irradiation (RT). We evaluated AZD2171, a highly potent, orally active, vascular endothelial growth factor (VEGF) signalling inhibitor, gefitinib, an EGFR tyrosine kinase inhibitor and RT. The antitumour efficacy of these treatments, administered alone and in combination for 2 weeks, was assessed in a VEGF-secreting human head and neck tumour cell line, CAL33 that highly expresses EGFR, established as xenografts (250 mm 3 ) in nude mice. The median time to reach a tumour volume of 1000 mm 3 was significantly increased for AZD2171 or gefitinib alone compared with the control. Greater inhibition of tumour growth was seen with the combination of AZD2171+gefitinib compared with either drug alone, and the triple combination compared with either AZD2171+gefitinib or RT alone. The intensity of endothelial cell staining was slightly reduced by each agent given alone, and markedly diminished by the double or triple combination. The triple combination almost completely abolished cell proliferation. The marked RT-induced enhancement in the DNA-repair enzyme ERCC1 expression was totally abolished by the triple combination. This observation could help to explain the supra-additive antitumour effect produced by this combination and could provide a basis for future innovative clinical trials.

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“…On the basis of these findings, it was proposed that overexpression of cortactin may contribute to increased EGFR expression and signalling in malignancies with CTTN amplification. This is of particular importance in HNSCC, since enhanced EGFR signalling/expression has been associated with aggressive disease and poor prognosis (Dassonville et al, 1993;Grandis and Tweardy, 1993;Kalyankrishna and Grandis, 2006) and EGFR-targeted molecular therapeutics are currently being examined in clinical settings (for recent reviews, see Astsaturov et al, 2006a, 2006band Reuter et al, 2007.…”

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Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

et al. 2008

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Cortactin is an actin-binding Src substrate involved in cell motility and invasion. In this study, we sought to examine the prognostic importance of cortactin protein expression in head and neck squamous cell carcinoma (HNSCC). To do so, cortactin and EGF receptor (EGFR) expression was retrospectively evaluated by immunohistochemistry in a tissue microarray composed of 176 HNSCCs with a mean follow-up time of 5 years. Cortactin immunoreactivity was weak to absent in normal epithelial tissue. Overexpression of the protein in 77 out of 176 tumours (44%) was associated with more advanced tumour-node-metastasis stage and higher histologic grade. Cortactin overexpression was associated with significantly increased local recurrence rates (49 vs 28% for high and low expressing carcinomas, respectively), decreased disease-free survival (17 vs 61%), and decreased the 5-year overall survival of (21 vs 58%), independently of the EGFR status. In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Importantly, we identified a subset of patients with cortactin-overexpressing tumours that displayed low EGFR levels and a survival rate that equalled that of patients with tumoral overexpression of both EGFR and cortactin. These findings identify cortactin as a relevant prognostic marker and may have implications for targeted therapies in patients with HNSCC.

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Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer.

Abstract: EGFR determination deserves particular attention in head and neck cancer, since it independently carries a strong prognostic value.

Cited by 372 publications

References 19 publications

Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

Dual inhibition of EGFR and VEGFR pathways in combination with irradiation: antitumour supra-additive effects on human head and neck cancer xenografts

Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

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