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Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions

1
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2
Faculty of Medicine, Benha University, Benha 13518, Egypt
3
School of Medicine, University of Washington, Seattle, WA 98195, USA
4
Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
5
Department of Urology, University of Washington, Seattle, WA 98195, USA
*
Author to whom correspondence should be addressed.
Cancers 2017, 9(12), 166; https://doi.org/10.3390/cancers9120166
Received: 13 October 2017 / Revised: 28 November 2017 / Accepted: 29 November 2017 / Published: 6 December 2017
Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa), suppression of systemic testosterone (T) has remained the most effective initial therapy for advanced disease although progression inevitably occurs. From the inception of clinical efforts to suppress androgen receptor (AR) signaling by reducing AR ligands, it was also recognized that administration of T in men with castration-resistant prostate cancer (CRPC) could result in substantial clinical responses. Data from preclinical models have reproducibly shown biphasic responses to T administration, with proliferation at low androgen concentrations and growth inhibition at supraphysiological T concentrations. Many questions regarding the biphasic response of PCa to androgen treatment remain, primarily regarding the mechanisms driving these responses and how best to exploit the biphasic phenomenon clinically. Here we review the preclinical and clinical data on high dose androgen growth repression and discuss cellular pathways and mechanisms likely to be involved in mediating this response. Although meaningful clinical responses have now been observed in men with PCa treated with high dose T, not all men respond, leading to questions regarding which tumor characteristics promote response or resistance, and highlighting the need for studies designed to determine the molecular mechanism(s) driving these responses and identify predictive biomarkers. View Full-Text
Keywords: high dose testosterone; supraphysiologic androgen; bipolar androgen therapy; biphasic; BAT; castration resistant prostate cancer; CRPC high dose testosterone; supraphysiologic androgen; bipolar androgen therapy; biphasic; BAT; castration resistant prostate cancer; CRPC
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MDPI and ACS Style

Mohammad, O.S.; Nyquist, M.D.; Schweizer, M.T.; Balk, S.P.; Corey, E.; Plymate, S.; Nelson, P.S.; Mostaghel, E.A. Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions. Cancers 2017, 9, 166. https://doi.org/10.3390/cancers9120166

AMA Style

Mohammad OS, Nyquist MD, Schweizer MT, Balk SP, Corey E, Plymate S, Nelson PS, Mostaghel EA. Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions. Cancers. 2017; 9(12):166. https://doi.org/10.3390/cancers9120166

Chicago/Turabian Style

Mohammad, Osama S.; Nyquist, Michael D.; Schweizer, Michael T.; Balk, Stephen P.; Corey, Eva; Plymate, Stephen; Nelson, Peter S.; Mostaghel, Elahe A. 2017. "Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions" Cancers 9, no. 12: 166. https://doi.org/10.3390/cancers9120166

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