RB1 and neoplasm: Using the Rb1 and Trp53 double–knockout organoid in vitro system, the authors found that the activation of JAK/STAT and FGF signaling is required for the transition from a luminal tumor cell phenotype to a multilineage, stem cell–like, and AR-independent state, but not for a fully redifferentiated NE-lineage trait, suggesting that an in vivo microenvironment is required to complete the AD-to-NE lineage transition (44, 45).