By analyzing perturbing mechanism in these two pathways, we identified several reversal gene pairs, including NRAS (neuroblastoma RAS) and CDK2 (cyclin-dependent kinase 2), CCND1 (cyclin D1) and FGFR (fibroblast growth factor receptor).
Taken together, this study suggests that CDK2 and CDK9 are potential therapeutic targets in NB and that abrogating CDK2 and CDK9 activity by small molecules like dinaciclib is a promising strategy and a treatment option for NB patients.
Targeted silencing of CDK2 by 3 RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells.
In previous preclinical studies, we have shown that targeted inhibition of cyclin-dependent kinase 2 (CDK2) resulted in specific killing of MYCN-amplified neuroblastoma cells.
This finding suggests that endogenous p21 protein in NB cells is inactive and may be bound either to a protein complex or in a conformation that precludes its binding to cdk2.