AR and neoplasm: Mechanistic explanations for AR hyperactivity in CRPC cells include: 1) increased AR expression (with or without concomitant AR gene amplification); 2) AR mutations that allow promiscuous activation by non-androgens; 3) expression of constitutively active truncated AR splice variants produced by alternate splicing [2]; 4) intratumoral steroidogenesis that generates a local tumor microenvironment enriched for testosterone/dihydrotestosterone; 5) tumor cell overexpression of AR co-activators that could further sensitize ARs in CRPC to castrate level androgens or alternate steroids.