1. The Aurora-Kinase A Phe31-Ile polymorphism as possible predictor of response to treatment in head and neck squamous cell carcinoma
- Author
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A Baumann, Dominik Schüttler, Gero Brockhoff, Guido Piontek, Lena Gebel, Martina Rudelius, M Buchberger, Anja Pickhard, Gerhard Piendl, and Rudolf Reiter
- Subjects
0301 basic medicine ,Cell ,HNSCC ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Aurora kinase ,Survivin ,medicine ,Aurora-Kinase ,neoplasms ,business.industry ,medicine.disease ,Head and neck squamous-cell carcinoma ,Aurora-Kinase a polymorphism ,inhibition ,ddc ,radiation ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,Docetaxel ,Tumor progression ,030220 oncology & carcinogenesis ,Alisertib ,Cancer research ,Aurora Kinase A ,business ,medicine.drug ,Research Paper - 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.
- Published
- 2018