RB1 and cancer: The p16/Rb/E2F regulatory pathway participates in cell cycle arrest and is inactivated in most human cancers, whereas p16INK4a is linked with CDK4 and CDK6 in competition with cyclin D1, which then prevents phosphorylation of the tumor-suppressor protein retinoblastoma (Rb), which contributes to form the pRbeE2F growth inhibitory complex and plays an important role in tumor pathogenesis [10].