AR and pachyonychia congenita: These therapies are effective in majority of patients, yet offer only a temporary relief, and the disease eventually recurs as treatment-resistant CRPC that is characterized by either AR loss-of function (treatment-emergent neuroendocrine PC, t-NEPC (4,5)) or gain-of-function, expressing AR variants (AR-Vs) with deleted LBD (AR-DLBD) (6).