Importantly, the licensing checkpoint is defective in many cancer cells, perhaps due to the involvement of p53, Rb, and p21Cip1, which are mutated or ineffective in many cancers (Shreeram et al., 2002, Feng et al., 2003, Montagnoli et al., 2004, Liu et al., 2009, Nevis et al., 2009, Blow and Gillespie, 2008). This evidence concerns the gene RB1 and cancer.