title: Cetuximab promotes epithelial to mesenchymal transition and cancer associated fibroblasts in patients with head and neck cancer.
abstract: OBJECTIVE
  To investigate if cetuximab induces epithelial to mesenchymal transition (EMT) and activation of cancer associated fibroblast (CAF) in the tumors of patients with squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Cetuximab was administered for two weeks prior to surgery to 20 treatment-naïve patients. Five untreated patients were included as controls. Tumor biopsies were performed at baseline and before surgery. Gene expression profiles and quantitative real-time PCR (qRT-PCR) analysis of the pre-and post-treatment biopsies were compared. To further investigate EMT and CAF, correlations between previously described EMT and CAF markers and our microarray data set were calculated.
  
  
  RESULTS
  Gene expression profile analyses and qRT-PCR showed that some of the genes modified by cetuximab were related to CAFs and EMT (ZNF521, CXCL12, ASPN, OLFML3, OLFM1, TWIST1, LEF1, ZEB1, FAP). We identified 2 patient clusters with different EMT and CAF characteristics. Whereas one cluster showed clear upregulation of expression of genes implicated in CAF and EMT including markers of embryologic pathways like NOTCH and Wnt, the other did not.
  
  
  CONCLUSIONS
  Even if EMT and CAFs are implicated in cetuximab resistance in pre-clinical models, we demonstrate for the first time that these molecular processes may occur clinically early on.
authors.affiliation: Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.|Department of Head and Neck Surgery, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmitz
authors.affiliation: INSERM UMRS1138, Laboratory of Integrative Cancer Immunology, Paris, France.|Université Paris Descartes, Rue de l'Ecole de Médecine, Paris, France.|Cordeliers Research Centre, Université Pierre et Marie Curie Paris, Paris, France.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bindea
authors.affiliation: Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Roxana Irina
authors.initials: RI
authors.lastname: Albu
authors.affiliation: INSERM UMRS1138, Laboratory of Integrative Cancer Immunology, Paris, France.|Université Paris Descartes, Rue de l'Ecole de Médecine, Paris, France.|Cordeliers Research Centre, Université Pierre et Marie Curie Paris, Paris, France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Mlecnik
authors.affiliation: Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.|Department of Head and Neck Surgery, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab / Q000627:therapeutic use*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab
keywords: anti-EGFR therapy; cancer-associated fibroblasts; epithelial-mesenchymal transition; head and neck cancer; pharmacodynamic