The biology of hormone refractory prostate cancer - Why does it develop?

To understand the biology of hormone refractory prostate cancer, it is crit ical to understand both the cellular organization of the normal prostate an d how normal prostate epithelial cells respond to androgen. Recent studies have demonstrated that the normal prostate is heterogenous, composed of ste m cell units hierarchically containing androgen-independent stem cells, and rogen-sensitive amplifying cells, and androgen-dependent transit epithelial cells. This article discusses the relationship between the specific cell. of origin for prostate cancer and the resulting androgen responsiveness of the cancer. In addition, various genetic and epigenetic mechanisms for the initial development and eventual clonal selection of androgen-sensitive and androgen-independent cancer cells from initially androgen-dependent prosta te cancer cells are presented. Therapeutic implications for such tumor cell heterogeneity and clonal selection are discussed.