Klin Padiatr 2012; 224 - A29
DOI: 10.1055/s-0032-1310496

Targeting PLK1 and Aurora kinases in medulloblastoma

M Holst 1, E Westerhout 3, M Kool 3, H Caron 2, R Versteeg 2, S Clifford 4, S Rutkowski 5, T Pietsch 1
  • 1Dept. Neuropathology, University Bonn
  • 2Dept. Pediatr., Oncology, AMC, Amsterdam
  • 3Dept. Human Genetics, AMC, Amsterdam
  • 4Northern Institute for Cancer Research, Newcastle
  • 5Dept. Pediatr. Oncology, Univ. Med. Center Hamburg-Eppendorf, Hamburg, Germany

Introduction: The Kids Cancer Kinome project is focussing on the human protein kinase family in pediatric tumors to identify and validate novel drug targets. We investigated medulloblastomas as most frequent malignant brain tumor.

Methods: We analysed the expression profiles (Affymetrix microarrays) of medulloblastoma tumor samples and cell lines. Using small molecules inhibitors and lentiviral particles carrying shRNA we examined the effects on cell proliferation (MTS assay), apoptosis (Caspase-glo assay) and cell cycle (flow cytometry).

Results: As promising candidates we identified the overexpressed Plk1 and Aurora kinases which are involved in cell cycle control and are altered in various cancer types. The inhibitors and shRNA caused a decrease of the cell proliferation an increased apoptosis as well as alterations of the cell cycle.

Conclusion: Inhibition of Plk1 or Aurora kinases represents a promising approach for novel targeted strategies in the treatment of medulloblastomas.