Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma.

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. 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. 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. Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma.