Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
BioMed CentralDate
2015-08-29Citation
10.1186/s12967-015-0633-7
Journal of Translational Medicine 13.282 (2015): 1-13
ISSN
1479-5876 (print); 1479-5876 (on line)DOI
10.1186/s12967-015-0633-7Funded by
The present work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) (AES Program, grant PI12/01552); the Ministerio de Sanidad (Cancer Network); the Comunidad de Madrid (S2010/BMD-2344). The Fundacion Jimenez Diaz Biobank is funded by a grant from the MINECO (Instituto de Salud Carlos III, RETICS Red de Biobancos, with FEDER funds, RD09/0076/00101). S.Z. and C.C. are supported by grants from the same Biobanks initiativeProject
Gobierno de España. PI12/01552; Comunidad de Madrid. S2010/BMD-2344/COLOMICS2Editor's Version
http://dx.doi.org/10.1186/s12967-015-0633-7Subjects
Cetuximab; EGFR; Head and neck squamous cell carcinoma (HNSCC); HGF; MET; Prognostic factor; MedicinaRights
© 2015 Madoz-Gúrpide et al.Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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
Files in this item
Google Scholar:Madoz-Gúrpide, Juan
-
Zazo, Sandra
-
Chamizo, Cristina
-
Casado, Victoria
-
Caramés, Cristina
-
Gavín, Eduardo
-
Cristóbal, Ion
-
García-Foncillas López, Jesús Miguel
-
Rojo, Federico
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
The hippo pathway transducers yap1/tead induce acquired resistance to trastuzumab in her2-positive breast cancer
González-Alonso, Paula; Zazo, Sandra; Martín-Aparicio, Ester; Luque, Melani; Chamizo, Cristina; Sanz-Álvarez, Marta; Minguez, Pablo; Gómez López, Gonzalo; Cristóbal, Ion; Caramés, Cristina; García-Foncillas López, Jesús Miguel; Eroles, Pilar; Lluch, Ana; Arpí, Oriol; Rovira, Ana; Albanell, Joan; Piersma, Sander R.; Jimenez, Connie R.; Madoz-Gúrpide, Juan; Rojo, Federico
2020-04-29