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

Mohammad, Osama and Nyquist, Michael and Schweizer, Michael and Balk, Stephen and Corey, Eva and Plymate, Stephen and Nelson, Peter and Mostaghel, Elahe (2017) Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions. Cancers, 9 (12). p. 166. ISSN 2072-6694

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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.

Item Type: Article or Abstract
DOI: 10.3390/cancers9120166
PubMed ID: 29210989
PMCID: PMC5742814
Depositing User: Allysha Eyler
Date Deposited: 25 Jan 2018 20:27
Last Modified: 25 Jan 2018 20:27

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