title: The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism.
abstract: OBJECTIVE
  The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines.
  
  
  METHODS
  First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples. The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting.
  
  
  RESULTS
  Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27).
  
  
  CONCLUSIONS
  This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany. Equal contribution.
authors: Anja
authors: A
authors: Pickhard
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany. Equal contribution.
authors: Michael
authors: M
authors: Siegl
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany.
authors: Alexander
authors: A
authors: Baumann
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany.
authors: Maximilian
authors: M
authors: Huhn
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany.
authors: Markus
authors: M
authors: Wirth
authors: Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany.
authors: Rudolf
authors: R
authors: Reiter
authors: Institute of Pathology, Julius-Maximilians-University and Comprehensive Cancer Center Mainfranken, Wuerzburg, German.
authors: Martina
authors: M
authors: Rudelius
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany.
authors: Guido
authors: G
authors: Piontek
authors: Department of Gynecology and Obstetrics; University of Regensburg, Regensburg, Germany.
authors: Gero
authors: G
authors: Brockhoff
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D000068818:Cetuximab; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D064096:Aurora Kinase A; D000068818:Cetuximab