Conversely, following RB1 loss, cancer can develop only if cells are intrinsically resistant to RB1-deficiency-induced apoptosis, or if cell death is counteracted by parallel activation of survival pathways, or, finally, if a second alteration, such as the abrogation of the p53 proapoptotic pathway (Fig. 1B), occurs during tumor development to allow cell expansion and cancer growth [28]. This evidence concerns the gene RB1 and cancer.