Here we focus on the CRPC-NE phenotype, an emerging and aggressive subtype of advanced prostate cancer that can arise as an androgen-independent mechanism of resistance to AR-directed therapies, due to the lack of approved therapies for patients, limited preclinical models (only one cell line is available through ATCC), and a still preliminary understanding of CRPC-NE biology. The gene discussed is AR; the disease is prostate cancer.