Prostate cancer stem cells: are they androgen-responsive?

The prostate gland is highly dependent on androgens for its development, growth and function. Consequently, the prostatic epithelium predominantly consists of androgen-dependent luminal cells, which express the androgen receptor at high levels. In contrast, androgens are not required for the survival of the androgen-responsive, but androgen-independent, basal compartment in which stem cells reside. Basal and luminal cells are linked in a hierarchical pathway, which most probably exists as a continuum with different stages of phenotypic change. Prostate cancer is also characterised by heterogeneity, which is reflected in its response to treatment. The putative androgen receptor negative cancer stem cell (CSC) is likely to form a resistant core after most androgen-based therapies, contributing to the evolution of castration-resistant disease. The development of CSC-targeted therapies is now of crucial importance and identifying the phenotypic differences between CSCs and both their progeny will be key in this process.