RB1 and cancer: Both the CDK4/6-Cyclin D and the CDK2-Cyclin E complexes serve as the central links in cell cycle regulation via regulating the G1–S transitions in cells, and abnormal activation of the CyclinD-CDK4/6–INK4–Rb pathway, which is often observed in various malignancies, will lead to uncontrolled growth of cancer cells (Sawai et al., 2012; The et al., 2015; VanArsdale et al., 2015).