RB1 and breast cancer: It is reported that the CDK4/6 relate to the regulation of the cell-cycle transition through retinoblastoma protein phosphorylation (pRb), while CDK2 contributes to the hyperphosphorylation of pRb and initiates DNA replication subsequently [54, 55] (Fig. 6d). Furthermore, a previous study showed the role of Rb phosphorylation in proliferation and apoptosis of tumor cells revealing the possibility of targeting Rb phosphorylation via CDK2 inhibitors in colon cancer [13], whereas some CDK4/6 inhibitors have been approved for the treatment of breast cancer [56].