Concurrent TP53 and RB1 defects are highly enriched in AR-independent neuroendocrine mCRPC compared with adenocarcinoma mCRPC.42 Combined TP53 and RB1 loss has been shown to promote lineage switching from an AR-dependent to an AR-independent state41,43,44 and consequent resistance to AR-targeted therapies. The gene discussed is RB1; the disease is adenocarcinoma.