Upon hypophosphorylation, Rb forms a complex with E2F and we show that treatment with palbociclib reduces the expression levels of E2F target genes involved in cell cycle progression, such as TOP2A, CCNE2, and TK1. Taken together, our results suggest that inhibition of CDK4/6 may provide an effective strategy to treat a subset of neuroblastoma tumors. Here, TOP2A is linked to neuroblastoma.