Most prostate cancers are androgen receptor (AR)-dependent; however, under sustained and potent AR pathway blockade, a subset can become AR-indifferent and instead rely on alternative programs, including FGF–MAPK signaling and neuroendocrine differentiation, as exemplified by neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC; AR−/NE−) [121,122]. Here, AR is linked to Familial prostate cancer.