Xenograft modeling of CRPC by serially propagating 4 AR+ human PCa models in castrated mice (which mimics first-line castration in patients using GnRH analogs18,19) reveals strikingly distinct evolutionary trajectories: the LNCaP model gradually becomes AR+/hi and VCaP and LAPC4 become nuc/cyto-AR whereas the LAPC9 model evolves into AR−/lo. The gene discussed is GNRH1; the disease is posterior cortical atrophy.