Resistance to these therapies may occur broadly through at least three mechanisms [6,10,12,15,24,32,33,34,35]: (1) AR-independent activation of AR-dependent pathways via bypass mechanisms, such as through up-regulation of glucocorticoid receptor expression [32]; (2) De-differentiation such as BRN2-mediated trans-differentiation to neuroendocrine prostate carcinoma [36]; and (3) The most commonly targeted mechanism, direct reactivation of the AR and its signaling despite castrate levels of androgens. This evidence concerns the gene AR and prostate neuroendocrine neoplasm.