RB1 and cancer: In addition to its well-characterized role in controlling S-phase entry, recent studies have revealed an expanded role for RB in impeding cancer aggressiveness, which has been underscored by results from genetically engineered mouse models, in which Rb1 loss facilitated lineage plasticity, metastasis, therapy resistance, and lethality of prostate and lung adenocarcinomas initiated by other genetic events (6, 12).