RT Journal Article
SR Electronic
T1 A Preclinical Xenograft Model Identifies Castration-Tolerant Cancer-Repopulating Cells in Localized Prostate Tumors
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 187ra71
OP 187ra71
DO 10.1126/scitranslmed.3005688
VO 5
IS 187
A1 Toivanen, Roxanne
A1 Frydenberg, Mark
A1 Murphy, Declan
A1 Pedersen, John
A1 Ryan, Andrew
A1 Pook, David
A1 Berman, David M.
A1 ,
A1 Taylor, Renea A.
A1 Risbridger, Gail P.
YR 2013
UL http://stm.sciencemag.org/content/5/187/187ra71.abstract
AB A lack of clinically relevant experimental models of human prostate cancer hampers evaluation of potential therapeutic agents. Currently, androgen deprivation therapy is the gold standard treatment for advanced prostate cancer, but inevitably, a subpopulation of cancer cells survives and repopulates the tumor. Tumor cells that survive androgen withdrawal are critical therapeutic targets for more effective treatments, but current model systems cannot determine when they arise in disease progression and are unable to recapitulate variable patient response to treatment. A model system was developed in which stromal-supported xenografts from multiple patients with early-stage localized disease can be tested for response to castration. The histopathology of these xenografts mimicked the original tumors, and short-term host castration resulted in reduced proliferation and increased apoptosis in tumor cells. After 4 weeks of castration, residual populations of quiescent, stem-like tumor cells remained. Without subsequent treatment, these residual cells displayed regenerative potential, because testosterone readministration resulted in emergence of rapidly proliferating tumors. Therefore, this model may be useful for revealing potential cellular targets in prostate cancer, which exist before the onset of aggressive incurable disease. Specific eradication of these regenerative tumor cells that survive castration could then confer survival benefits for patients.