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Westerhout, Ellen M.; Kool, Marcel; Molenaar, Jan J.; Boer den, Monique L.; Clifford, Steve C.; Delattre, Olivier; Geoerger, Birgit; Lanvers, Claudia; Pietsch, Torsten; Serra, Massimo; Shipley, Janet; Vassal, Gilles; Versteeg, Rogier; Verschuur, Arnauld C.; Caron, Huib N.

Abstract C115: The KidsCancerKinome: Validation of Aurora kinases as potential drug targets in pediatric tumors

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  • Medientyp: E-Artikel
  • Titel: Abstract C115: The KidsCancerKinome: Validation of Aurora kinases as potential drug targets in pediatric tumors
  • Beteiligte: Westerhout, Ellen M.; Kool, Marcel; Molenaar, Jan J.; Boer den, Monique L.; Clifford, Steve C.; Delattre, Olivier; Geoerger, Birgit; Lanvers, Claudia; Pietsch, Torsten; Serra, Massimo; Shipley, Janet; Vassal, Gilles; Versteeg, Rogier; Verschuur, Arnauld C.; Caron, Huib N.
  • Erschienen: American Association for Cancer Research (AACR), 2009
  • Erschienen in: Molecular Cancer Therapeutics
  • Sprache: Englisch
  • DOI: 10.1158/1535-7163.targ-09-c115
  • ISSN: 1535-7163; 1538-8514
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>The KCK consortium has validated Aurora kinase A and B as potential drug targets in six highly malignant pediatric tumor types (i.e Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, neuroblastoma, medulloblastoma and ALL). The stepwise procedure started with the extensive analyses of expression of human kinases using Affymetrix mRNA profiles of over 500 tumors and cell lines. Clustering analyses on the combined data of all tumor types revealed a cluster containing many G2M kinases that showed significantly higher expression patterns than in the reference tissues. Prominently present in the G2M cluster were Aurora kinase A and B, which expression could be correlated to poor prognosis in the individual tumor types in further analyses. Subsequently, lentiviral shRNA-mediated knockdown of AURKA and AURKB protein expression has been performed in cell line panels for each tumor type to evaluate the kinases for their potential as drug targets. Inhibition of the Aurora kinases resulted in significant phenotypes in several pediatric tumor cell lines ranging from growth inhibition to extensive cell death. The knockdown of AURKA or AURKB often leads to induction of apoptosis, although preceded by a different type of cell arrest. These findings were promising for further evaluation of Aurora kinase inhibitors in the core panel of sensitive pediatric tumor cell lines.</jats:p> <jats:p>Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C115.</jats:p>
  • Zugangsstatus: Freier Zugang