CDK4 and neoplasm: Stress-induced cellular senescence primarily involves two pathways: the p53-p21-DREAM-CDE/CHR pathway, where p53, a tumor suppressor, indirectly halts cell cycle progression and reduces gene expression, resulting in cell cycle arrest, apoptosis, or senescence [4, 46-49]; and the p16-CDK4/6-Rb pathway, where p16, an inhibitor of CDK4/6, regulates cell cycle arrest by influencing the phosphorylation state of the Rb protein [50, 51].