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

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.

Impact of HPV Status and AurkA Phe31Ile Polymorphism on The Response to Cetuximab Treatment of Head and Neck Squamous Cell Carcinoma (HNSCC) Patients

“…In contrast, we observed an enormous increase in heterozygous cells in an aneuploid (i.e., tetraploid) state. This nding con rms previous work performed on SAS and UD-SCC-5 cells treated with different inhibitors [62]. Most importantly, the formation of aneuploid cells occurred only in a heterozygous HN cell line (i.e., HN cells).…”

“…Although Royce et al detected Aurora kinase A overexpression in the tumor tissue, this did not correlate with the prognosis of the patients [76]. Results from our research group con rm this, as there was no detectable association between the Aurora kinase A polymorphism and overall patient survival [62,39]. However, the literature clearly raises suspicion that the Aurora kinase A polymorphism signi cantly increases the risk of developing malignancy [77], and also plays a crucial role in the response to treatment.…”

“…In the subsequent work of 2018, the relevance of the Aurora kinase A polymorphism in terms of therapeutic response was con rmed in vitro. Correlation analyzes revealed a signi cantly better response to speci c inhibition therapy in the AurkA heterozygous Phe/Ile cell line [62].…”

AURKA rs2273535 T>A Polymorphism Associated With Cancer Risk: A Systematic Review With Meta-Analysis

“…Forty evaluation items related to quality assessment were used in meta-analysis, with scores ranging from 0 to 40. Based on the STROBE score, the included studies were classified as low quality (0-19), moderate quality (20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and high quality (30-40) ( 10). If the studies were of low quality, moderate, or high quality, they were considered to be at high, moderate or low risk of bias, respectively.…”

Effects of AURKA‐mediated degradation of SOD2 on mitochondrial dysfunction and cartilage homeostasis in osteoarthritis

“…Baumann et al, 2018;Hou et al, 2018). As a biomarker and F I G U R E 6 Ubiquitination of AURKA mediates the occurrence of OA via degradation of SOD2 Note: (a) ubiquitin chain K48 binding protein detected using the IP experiment; IB:SOD2, IB:UB, SOD2 was present in the K48 immunoprecipitates (b), AURKA binds to SOD2 in the IP experiment, IB:SOD2, IB:UB, SOD2 was present in the AURKA immunoprecipitates; (c) Ubiquitination expression in OA rat bone joint tissues using immunohistochemistry.…”