The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

Anja Pickhard; Michael Siegl; Alexander Baumann; Maximilian Huhn; Markus Wirth; Rudolf Reiter; Martina Rudelius; Guido Piontek; Gero Brockhoff

doi:10.18632/oncotarget.2117

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Research Papers:

The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

Anja Pickhard _, Michael Siegl, Alexander Baumann, Maximilian Huhn, Markus Wirth, Rudolf Reiter, Martina Rudelius, Guido Piontek and Gero Brockhoff

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Oncotarget. 2014; 5:5428-5438. https://doi.org/10.18632/oncotarget.2117

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Abstract

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

Correspondence:

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

Abstract

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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Research Papers:

The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

Abstract