To further validate whether ectopic JAK–STAT is required for resistance in human PCa, we surveyed a series of three-dimensional (3D)-cultured human-derived organoid (PDO) models (Extended Data Fig. 6a)53–55 and observed ectopic upregulation of JAK–STAT signaling genes in PDOs with TP53/RB1 deficiency (Extended Data Fig. 6b). Here, RB1 is linked to posterior cortical atrophy.