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The Aurora-Kinase A Phe31-Ile polymorphism as possible predictor of response to treatment in head and neck squamous cell carcinoma
- Source :
- Oncotarget
- Publication Year :
- 2018
- Publisher :
- Impact Journals LLC, 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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 9
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....8e19b8ecd9c8dfda697e84cfef2bddd8