Prostate cancer stem cells: The case for model systems

Advanced prostate cancers are treated with androgen deprivation therapy, which usually leads to a rapid and significant reduction in tumor burden but subsequent development of castration-resistant and metastatic disease almost always occurs. The source of tumor heterogeneity and the accompanying mechanisms leading to treatment resistance are major areas of prostate cancer research. Although our understanding of tumor heterogeneity is evolving, the functional isolation of tumor propagating populations, also known as cancer stem cells (CSCs), is fundamental to the identification and molecular characterization of castration-resistant prostate cancer cells. Of clinical importance, knowledge of prostate CSCs has implications for design of next generation-targeted therapies aimed at both eradicating primary tumor mass and preventing castration-resistant disease. The inability to routinely transplant fractionated primary human prostate tumors has prevented progress in analyzing the source of heterogeneous and treatment-resistant populations in prostate cancer. Here, we briefly overview the mechanisms of castration resistance, including the hypothesis for the existence of androgen-independent prostate CSCs. Finally, we discuss the interpretation of preclinical models and their utility for characterizing prostate CSCs in androgen-replete and androgen-deprived conditions.