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dc.contributor.authorScharer, Christopher D.en_US
dc.contributor.authorLaycock, Noelanien_US
dc.contributor.authorOsunkoya, Adeboye O.en_US
dc.contributor.authorLogani, Sanjayen_US
dc.contributor.authorMcDonald, John F.en_US
dc.contributor.authorBenigno, Benedict B.en_US
dc.contributor.authorMoreno, Carlos S.en_US
dc.date.accessioned2010-04-21T14:03:59Z
dc.date.available2010-04-21T14:03:59Z
dc.date.issued2008-12-11
dc.identifier.citationChristopher D. Scharer, Noelani Laycock, Adeboye O. Osunkoya, Sanjay Logani, John F. McDonald, Benedict B. Benigno, and Carlos S. Moreno, "Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells," Journal of Translational Medicine 2008, 6:79.en_US
dc.identifier.issn1479-5876
dc.identifier.urihttp://hdl.handle.net/1853/32529
dc.description© 2008 Scharer et al; licensee BioMed Central Ltd. The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/6/1/79en_US
dc.descriptionDOI:10.1186/1479-5876-6-79
dc.description.abstractBackground: A large percentage of patients with recurrent ovarian cancer develop resistance to the taxane class of chemotherapeutics. While mechanisms of resistance are being discovered, novel treatment options and a better understanding of disease resistance are sorely needed. The mitotic kinase Aurora-A directly regulates cellular processes targeted by the taxanes and is overexpressed in several malignancies, including ovarian cancer. Recent data has shown that overexpression of Aurora-A can confer resistance to the taxane paclitaxel. Methods: We used expression profiling of ovarian tumor samples to determine the most significantly overexpressed genes. In this study we sought to determine if chemical inhibition of the Aurora kinase family using VE-465 could synergize with paclitaxel to induce apoptosis in paclitaxel-resistant and sensitive ovarian cancer cells. Results: Aurora-A kinase and TPX2, an activator of Aurora-A, are two of the most significantly overexpressed genes in ovarian carcinomas. We show that inhibition of the Aurora kinases prevents phosphorylation of a mitotic marker and demonstrate a dose-dependent increase of apoptosis in treated ovarian cancer cells. We demonstrate at low doses that are specific to Aurora-A, VE-465 synergizes with paclitaxel to induce 4.5-fold greater apoptosis than paclitaxel alone in 1A9 cells. Higher doses are needed to induce apoptosis in paclitaxel-resistant PTX10 cells. Conclusion: Our results show that VE-465 is a potent killer of taxane resistant ovarian cancer cells and can synergize with paclitaxel at low doses. These data suggest patients whose tumors exhibit high Aurora-A expression may benefit from a combination therapy of taxanes and Aurora-A inhibition.en_US
dc.language.isoen_USen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectAurora-A inhibitionen_US
dc.subjectChemotherapeuticsen_US
dc.subjectTaxane resistant ovarian cancer cellsen_US
dc.subjectVE-465en_US
dc.subjectRecurrent ovarian canceren_US
dc.titleAurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cellsen_US
dc.typeArticleen_US
dc.contributor.corporatenameGeorgia Institute of Technology. School of Biologyen_US
dc.contributor.corporatenameEmory University. Dept. of Pathology and Laboratory Medicineen_US
dc.contributor.corporatenameEmory University. Program in Genetics and Molecular Biologyen_US
dc.contributor.corporatenameGeorgia Institute of Technology. Ovarian Cancer Instituteen_US
dc.contributor.corporatenameWinship Cancer Institute of Emory Universityen_US
dc.publisher.originalBioMed Central
dc.identifier.doi10.1186/1479-5876-6-79


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