Using both pre-clinical models and pre-treatment biopsies from a recently completed ZEN-3694 BET bromodomain inhibitor clinical trial (55), we determined that a subset of NEPC tumors harboring high expression of the AR-repressed, E2F1-activated NEPC lineage plasticity program we identified in MR42D cells was strongly linked to prolonged tumor control with BET bromodomain inhibitor treatment. The gene discussed is AR; the disease is neoplasm.