Research ArticleProstate Cancer

A Preclinical Xenograft Model Identifies Castration-Tolerant Cancer-Repopulating Cells in Localized Prostate Tumors

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Science Translational Medicine  29 May 2013:
Vol. 5, Issue 187, pp. 187ra71
DOI: 10.1126/scitranslmed.3005688

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The Enemy Within

Prostate cancer is one of the most common types of cancer in men. In advanced stages, it is typically treated with medications that mimic castration, depriving the tumor of androgen stimulation. Unfortunately, these cancers eventually become castration-resistant and begin to grow even in the absence of hormonal input. What isn’t known is how these cancer cells develop the ability to survive androgen deprivation, and whether some types of stem-like castration-resistant cells are already present in prostate cancer from early stages or evolve later during the course of treatment. Now, Toivanen and colleagues shed some light on this mystery, with a report of castration-tolerant cells derived from early localized tumors that had not yet been exposed to anti-androgen therapy.

The authors used primary prostate tumors from 12 men with localized cancer, implanting them in a mouse xenograft model to study the effects of androgen deprivation on the tumors’ survival. Castration of the host mice led to rapid regression, but not disappearance of the tumors. Even after a prolonged period of castration (4 weeks), some residual tumor foci persisted. When testosterone stimulation was restored in the host animals, these residual cells rebounded, regenerating masses that were histologically similar to the original tumors.

This work by Toivanen et al. indicates that some prostate cancer cells can survive castration and later repopulate the tumor when androgen stimulation is available. Thus far, there is no indication that these castration-tolerant cells can proliferate in the absence of androgens, unlike the cells found in more advanced “castration-resistant” prostate cancer. Additional work will be needed to clarify whether these might be a type of prostate cancer stem cells, and what makes them different from the population of “androgen-sensitive” cancer cells that do not survive androgen depletion. Although there are many questions that must still be answered about the biology of these castration-tolerant cells, this work raises the intriguing possibility that we may eventually be able to specifically target and eradicate them, thus preventing prostate cancer recurrence in patients.