The Response of Head and Neck Squamous Cell Carcinoma to Cetuximab Treatment Depends on Aurora Kinase A Polymorphism

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Jul 2

PMID 24980817

Citations 11

Authors

Anja Pickhard

Michael Siegl

Alexander Baumann

Maximilian Huhn

Markus Wirth

Rudolf Reiter

Martina Rudelius

Guido Piontek

Gero Brockhoff

Affiliations

Soon will be listed here.

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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