Aurora kinase A as a rational target for therapy in glioblastoma

Laboratory investigation

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Object

Despite advances in the knowledge of tumor biology, the outcome of glioblastoma tumors remains poor. The design of many molecularly targeted therapies in glioblastoma has focused on inhibiting molecular abnormalities present in tumor cells compared with normal tissue rather than patient outcome-associated factors. As an alternative approach, the present study identified genes associated with shorter survival as potential therapeutic targets. It was hypothesized that inhibition of a molecular target associated with poor outcome would impact glioblastoma cell proliferation.

Methods

The present study correlated patient survival data with tumor gene expression profiling and gene ontology analysis. Genes associated with shorter survival were identified and one of these was selected for therapeutic targeting in an in vitro system. Glioblastoma cell growth suppression was measured by H3-thymidine uptake, colony formation, and flow cytometry.

Results

The gene expression microarray and ontology analysis revealed that genes involved in mitotic processes, including AURKA, were associated with poor prognosis in glioblastoma. Inhibition of AURKA suppressed glioblastoma cell growth. Moreover, inhibition of AURKA was synergistic with radiation in glioblastoma cells at high radiation doses.

Conclusions

Relative expression of AURKA may be of prognostic value and warrants further investigation with larger, prospective studies. Pharmacological inhibition of AURKA is a potentially promising therapy for glioblastoma.

Abbreviations used in this paper: GOTERM = Gene Ontology Project term; HGG = high-grade glioma; IC50 = half maximal inhibitor concentration; NHA = normal human astrocyte; qRT-PCR = quantitative real-time polymerase chain reaction.
Article Information

Contributor Notes

Address correspondence to: Valerie N. Barton, B.A., University of Colorado Denver, Department of Pediatrics, Mail Stop 8302, P.O. Box 6511, Aurora, Colorado 80045. email: valerie.barton@ucdenver.edu.

© AANS, except where prohibited by US copyright law.

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