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

Pickhard, Anja and Siegl, Michael and Baumann, Alexander and Huhn, Maximilian and Wirth, Markus and Reiter, Rudolf and Rudelius, Martina and Piontek, Guido and Brockhoff, Gero (2014) The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism. ONCOTARGET, 5 (14). pp. 5428-5438. ISSN 1949-2553,

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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.

Item Type: Article
Uncontrolled Keywords: CHROMOSOMAL INSTABILITY; TUMOR PROGRESSION; CANCER; OVEREXPRESSION; GENE; EXPRESSION; BREAST; SUSCEPTIBILITY; CHEMOTHERAPY; ASSOCIATION; Aurora kinase A polymorphism; Aurora kinase B; cetuximab; HNSCC
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 12 Sep 2019 09:21
Last Modified: 12 Sep 2019 09:21
URI: https://pred.uni-regensburg.de/id/eprint/9861

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