However, the long-term use of CDK4/6 inhibitors results in drug resistance and poor therapeutic effect on Rb-deficient tumors, especially some malignant tumors, which limits the clinical application of CDK4/6 inhibitors (Braal et al., 2021; Gomatou et al., 2021; Julve et al., 2021). The gene discussed is CDK4; the disease is cancer.