RB1 and neoplasm: This notion was reinforced when tumor cells expressing wild-type Rb were found to have genetic and epigenetic alterations of the p16 tumor suppressor gene or oncogenic expression of cyclin D1, D2, D3, Cdk4, and Cdk6 genes, which became known as the ‘p16-cyclin D-Rb’ pathway (Sherr, 1994; Sherr and McCormick, 2002; Burkhart and Sage, 2008; Paternot et al., 2010; Henley and Dick, 2012; Choi and Anders, 2013).