Next Article in Journal
Tracking Functional Tumor Cell Subpopulations of Malignant Glioma by Phasor Fluorescence Lifetime Imaging Microscopy of NADH
Previous Article in Journal
Ubiquitin Specific Peptidase 22 Regulates Histone H2B Mono-Ubiquitination and Exhibits Both Oncogenic and Tumor Suppressor Roles in Cancer
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessReview
Cancers 2017, 9(12), 166; https://doi.org/10.3390/cancers9120166

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.
Received: 13 October 2017 / Revised: 28 November 2017 / Accepted: 29 November 2017 / Published: 6 December 2017
Full-Text   |   PDF [876 KB, uploaded 6 December 2017]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top