RB1 and cancer: Although the main mechanism of action is thought to be suppression of RB protein phosphorylation followed by cell-cycle arrest, CDK4/6 kinase inhibitors alter cancer cell biology by means that go well beyond cell-cycle inhibition including modulation of mitogenic kinase signaling, induction of apoptosis, rewiring of transcriptional networks, induction of differentiation, and enhancement of cancer cell immunogenicity that can also be leveraged for therapeutic benefit [26,27,31,41].