AR and Familial prostate cancer: The underlying mechanisms that account for the ultimate emergence of resistance to androgen deprivation therapy (ADT), progressing to castrate-resistant prostate cancer (CRPC), and to second generation androgen blockade, include those that reactivate androgen receptor (AR) signaling despite strong inhibition (e.g., AR amplification and/or mutation), or those that are entirely independent or cooperate with androgen signaling to underlie PCa progression [1].