Androgen-deprivation remains an important therapeutic option for prostate cancer, and thus castration-resistance is lethal. Despite intense efforts to understand the mechanisms of therapy resistance, the underlying cells remain ill described. We now describe in wild-type (WT) mouse prostates a rare population of luminal progenitor cells that tolerate androgen deprivation and persist or are enriched 2-3 weeks after castration. The tumor-initiating properties of these cells areshown by regeneration of tumors in vivoand their gene-expression profile distinguishes them from luminal and basal/stem cells. Their intrinsic androgen signaling is markedly decreased and they are a probable source of prostate cancer relapse after androgen deprivation and thus might constitute a new therapeutic target for the prevention of castration-resistant prostate cancer.
This report was now published by an international consortium with contributions by Lukas Kenner and Richard Moriggl in the Journal of Pathology.