Concurrently, CDK4/6 overexpression reduces drug efficacy, as shown in CDK4-amplified alveolar rhabdomyosarcoma and glioma models, while CDK6 upregulation in resistant MCF-7 cells restores Rb phosphorylation capacity (Olanich et al., 2015; Cen et al., 2012; Ogata et al., 2021; Yang et al., 2017). The gene discussed is CDK4; the disease is central nervous system cancer.