title: Evaluation of FGFR3 as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma.
abstract: Although head and neck squamous cell carcinoma (HNSCC) is the sixth most common tumour entity worldwide, it remains a clinical challenge. Large-scale explorative genomic projects have identified several genes as potential targets for therapy, including fibroblast growth factor receptor 3 (FGFR3).
  
  
  
  The aim of this study was to investigate the biological significance of wild-type and mutated FGFR3 to evaluate its potential as a novel therapeutic target in HNSCC.
  
  
  
  FGFR3 protein expression was analysed in a large HNSCC tissue cohort (n = 536) and FGFR3 mRNA expression from The Cancer Genome Atlas (TCGA; n = 520). Moreover, FGFR3 wild-type and mutant versions were overexpressed in vitro, and both proliferation and migration was assessed with and without BGJ398 (a specific FGFR1-3 inhibitor) treatment.
  
  
  
  Although FGFR3 expression for both cohorts decreased during tumour progression, high FGFR3 expression levels were observed in a small subset of patients. In vitro, FGFR3 overexpression led to increased proliferation, whereas migration was not altered. Moreover, FGFR3-overexpressing cells were more sensitive to BGJ398. Cells overexpressing FGFR3 mutant versions showed increased proliferation compared to wild-type FGFR3 under serum-reduced conditions and were largely as sensitive as the wild-type protein to BGJ398.
  
  
  
  Taken together, the results of this study demonstrate that although FGFR3 expression decreases during HNSSC progression, it plays an important role in tumour cell proliferation and thus may be a potential target for therapy in selected patients suffering from this dismal tumour entity.
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: von Mässenhausen
authors.affiliation: Pathology of the University Hospital of Luebeck, Luebeck, Germany.|Department of Pathology, Leibniz Research Center Borstel, Borstel, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Deng
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Billig
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Queisser
authors.affiliation: Pathology of the University Hospital of Luebeck, Luebeck, Germany.|Department of Pathology, Leibniz Research Center Borstel, Borstel, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröck
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Göke
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Franzen
authors.affiliation: Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Heasley
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Pathology of the University Hospital of Luebeck, Luebeck, Germany. Sven.Perner@uksh.de.|Department of Pathology, Leibniz Research Center Borstel, Borstel, Germany. Sven.Perner@uksh.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D051498:Receptor, Fibroblast Growth Factor, Type 3