Oncotarget

Research Papers:

The Aurora-Kinase A Phe31-Ile polymorphism as possible predictor of response to treatment in head and neck squamous cell carcinoma

Alexander Baumann, Maria S. Buchberger, Guido Piontek, Dominik Schüttler, Martina Rudelius, Rudolf Reiter, Lena Gebel, Gerhard Piendl, Gero Brockhoff, Anja Pickhard _

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Oncotarget. 2018; 9:12769-12780. https://doi.org/10.18632/oncotarget.24355

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Abstract

Alexander Baumann1, Anna Maria S. Buchberger2,*, Guido Piontek2, Dominik Schüttler3, Martina Rudelius4, Rudolf Reiter5, Lena Gebel6, Gerhard Piendl6, Gero Brockhoff6 and Anja Pickhard2

1Department of Otolaryngology Head and Neck Surgery, Helios Amper-Klinikum Dachau, Dachau, Germany

2Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Munich, Germany

3Medizinische Klinik und Poliklinik I, University of Munich, Munich, Germany

4Institute of Pathology, University of Düsseldorf, Düsseldorf, Germany

5Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany

6University Medical Center Regensburg, Department of Gynecology and Obstetrics, Regensburg, Germany

*This author contributed equally to this work

Correspondence to:

Anja Pickhard, email: a.pickhard@lrz.tum.de

Keywords: HNSCC; Aurora-Kinase; Aurora-Kinase a polymorphism; radiation; inhibition

Received: February 06, 2017     Accepted: December 10, 2017     Published: January 30, 2018

ABSTRACT

Recently the Aurora-Kinases (Aurk) moved into the focus as novel disease related biomarkers and therapeutic targets. Elevated Aurora-Kinase expression has been found in a number of malignancies, amongst them HNSCC. For esophageal cancer, the AurkA Phe31-Ile polymorphism has previously been associated with tumor progression. Here we evaluated the treatment efficiency of HNSCC cell radiation as a function of Aurora-Kinases in HNSCC cell lines. Moreover, we investigated a potential sensitization to radiation by a cell treatment with the inhibitors Alisertib, Barasertib, Docetaxel and VX-680.

In parallel the radiation dependent expression and regulation of AurkA/B, p-Akt Ser 473 and Survivin and the AurkA polymorphism were investigated in primary tumor samples. We identified a high-risk collective with elevated AurkA and Survivin or AurkA and p-Akt Ser 473 expression.

High AurkA, AurkB, and p-Akt Ser 473 expression was exclusively found in the heterozygous cell line. We found a polymorphism dependent sensitivity to treatments with different Aurk inhibitors: The homozygous cell line UD-SCC-5 could be sensitized to radiation with Docetaxel in combination with any of the Aurora-Kinase inhibitors. In contrast, treatment with Docetaxel or radiation did not enhance the inhibitory effect of Barasertib or VX-680 in the heterozygous SAS cell line.

These findings indicate that the Aurora-Kinase A Phe31-Ile-polymorphism is a possibly predictive factor for response to radiation in combination with Docetaxel and Aurora-Kinase inhibitor treatments.


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