title: Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma.
abstract: BACKGROUND
  Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target.
  
  
  METHODS
  In this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells.
  
  
  RESULTS
  Marked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway.
  
  
  CONCLUSIONS
  Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma.
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Ali
authors.initials: A
authors.lastname: Rihani
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van Maerken
keywords: Cell cycle; Cyclin D1; Neuroblastoma; Palbociclib; Targeted therapy