AR and cancer: There are at least 2 potential mechanisms to explain this phenomenon and the emergence of ARSi-resistant DNPC: (a) an initially AR+ cancer–initiating cell loses AR expression under ADT and acquires this phenotypic heterogeneity via lineage plasticity (i.e., adaptation); or (b) an AR– prostate progenitor cell is the cancer-initiating cell and gives rise to malignant progeny heterogeneously expressing various combinations of basal and luminal markers (i.e., selection).