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Prostate Cancer Stem Cells: A New Target for Therapy

Norman J. Maitland, Anne T. Collins

From the YCR Cancer Research Unit, Department of Biology, University of York, York, United Kingdom

Corresponding author: Norman J. Maitland, BsC, PhD, YCR Cancer Research Unit, Department of Biology, University of York, Heslinton, York, YO10 5YW, United Kingdom; e-mail: njm9{at}york.ac.uk

The existence of prostate cancer stem cells offers a theoretical explanation for many of the enduring uncertainties surrounding the etiology and treatment of the most commonly diagnosed tumor in US males. The study of cancer stem cells in prostate, as in other complex tissues, is critically dependent on the availability of pure cell populations, a situation complicated by the heterogeneity of prostate tumors. However, selection of cells with a CD133⁺/2β1 integrin/ CD44⁺ phenotype enriches for a tumor-initiating population from human prostate cancers. Among the most pressing needs is for enduring therapy in patients who have experienced failure of hormonal treatments. Because the putative cancer stem cell does not express androgen receptor, it is likely to be immune from most androgen-based therapies, and an inherent genetic instability would enable the tumor to develop the new variants present in hormone-refractory disease. Prostate cancer stem cells have a unique gene expression signature that can also be related to Gleason grade and patient outcome. The scarcity of cancer stem cells in a prostate tumor will probably limit their usefulness in cancer diagnosis and prognosis. However, the emergence of new stem-cell therapeutic targets not only will require new assays for efficacy (because of their relatively quiescent nature), but also holds real promise of more lasting treatments to augment those currently directed against the remaining tumor cells, which comprise 99.9% of tumor mass, but paradoxically have a poor tumor-initiating capacity.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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