The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
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Anja Pickhard1,*, Michael Siegl1,*, Alexander Baumann1, Maximilian Huhn1, Markus Wirth1, Rudolf Reiter2, Martina Rudelius3, Guido Piontek1 and Gero Brockhoff4
1 Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany
2 Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany
3 Institute of Pathology, Julius-Maximilians-University and Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany
4 Department of Gynecology and Obstetrics; University of Regensburg, Regensburg, Germany
* Equal contribution
Anja Pickhard, email:
Keywords: Aurora kinase A polymorphism, Aurora kinase B, cetuximab, HNSCC
Received: May 1, 2014 Accepted: June 17, 2014 Published: June 18, 2014
Objectives: 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.
Materials and 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).
Conclusion: 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.
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