Moreover, our in vivo data demonstrated that in a pediatric patient-derived xenograft (PDX) model of relapsed OS that exhibited CDK4/6 hyperactivation, the dual inhibition of the CDK4/6 and PI3K/mTOR pathways was well tolerated and tumor growth was significantly decreased, compared to single agents (Barghi et al., unpublished observations). This evidence concerns the gene CDK4 and neoplasm.