TY  - JOUR
A1  - Pickhard, Anja
A1  - Siegl, Michael
A1  - Baumann, Alexander
A1  - Huhn, Maximilian
A1  - Wirth, Markus
A1  - Reiter, Rudolf
A1  - Rudelius, Martina
A1  - Piontek, Guido
A1  - Brockhoff, Gero
T1  - The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
JF  - Oncotarget
N2  - 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.
KW  - aurora kinase A polymorphism
KW  - aurorakinase B
KW  - cetuximab
KW  - HNSCC
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120757
VL  - 5
IS  - 14
ER  -