Although the sensitivity of RCC cells to CDK4/6 inhibitors is associated with many factors, including expression of p16, p15, Rb1, and E2F1 [21], we speculate that the possible reason for the selectivity between normal and RCC cells might be that normal cells are less dependent on the CDK4/6-p16-Rb axis for proliferation and survival than RCC cells. This evidence concerns the gene E2F1 and renal cell carcinoma.