The conversion of reversible G1 arrest to a senescent phenotype in response to CDK4/6 inhibition occurs in a subset of cell lines and primary cancers and has been linked to downregulation of the MDM2 protein, dependent on its E3 ligase activity, as well as on the presence of ATRX, which likely converge on expression and stabilization of a senescence-activating protein [41]. Here, CDK4 is linked to cancer.