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Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer.


ABSTRACT: Activation of the MET oncogene promotes tumor growth, invasion and metastasis in several tumor types. Additionally, MET is activated as a compensatory pathway in the presence of EGFR blockade, thus resulting in a mechanism of resistance to EGFR inhibitors.We have investigated the impact of HGF and MET expression, MET activation (phosphorylation), MET gene status, and MET-activating mutations on cetuximab sensitivity in recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) patients.A single-institution retrospective analysis was performed in 57 patients. MET overexpression was detected in 58% patients, MET amplification in 39% and MET activation (p-MET) in 30%. Amplification was associated with MET overexpression. Log-rank testing showed significantly worse outcomes in recurrent/metastatic, MET overexpressing patients for progression-free survival and overall survival. Activation of MET was correlated with worse PFS and OS. In multivariate logistic regression analysis, p-MET was an independent prognostic factor for PFS. HGF overexpression was observed in 58% patients and was associated with MET phosphorylation, suggesting a paracrine activation of the receptor.HGF/MET pathway activation correlated with worse outcome in recurrent/metastatic HNSCC patients. When treated with a cetuximab-based regimen, these patients correlated with worse outcome. This supports a dual blocking strategy of HGF/MET and EGFR pathways for the treatment of patients with recurrent/metastatic HNSCC.

SUBMITTER: Madoz-Gurpide J 

PROVIDER: S-EPMC4552997 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer.

Madoz-Gúrpide Juan J   Zazo Sandra S   Chamizo Cristina C   Casado Victoria V   Caramés Cristina C   Gavín Eduardo E   Cristóbal Ion I   García-Foncillas Jesús J   Rojo Federico F  

Journal of translational medicine 20150829


<h4>Background</h4>Activation of the MET oncogene promotes tumor growth, invasion and metastasis in several tumor types. Additionally, MET is activated as a compensatory pathway in the presence of EGFR blockade, thus resulting in a mechanism of resistance to EGFR inhibitors.<h4>Methods</h4>We have investigated the impact of HGF and MET expression, MET activation (phosphorylation), MET gene status, and MET-activating mutations on cetuximab sensitivity in recurrent or metastatic squamous cell carc  ...[more]

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