CDK4 and neuroblastoma: The p-Rb results in the release of active nuclear transcription factor E2F which enters the nucleus, binds to a series of promoter regions, promotes downstream gene expression, and drives the progression of the G1-to-S cell cycle.24 The role of CDK4 via p-Rb in G1-to-S cell cycle progression is consistent with our study, in which we have shown that BEZ235 downregulates CDK4 protein, decreases p-Rb and thus induces G0/G1 cell cycle arrest in NB cells (Figure 1).