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. 2011 May;6(3):483-493.
doi: 10.1586/eem.11.33.

Outsmarting androgen receptor: creative approaches for targeting aberrant androgen signaling in advanced prostate cancer

Karen E Knudsen  1 , William Kevin Kelly
Affiliations

Outsmarting androgen receptor: creative approaches for targeting aberrant androgen signaling in advanced prostate cancer

Karen E Knudsen et al. Expert Rev Endocrinol Metab. 2011 May.

Abstract

Prostatic adenocarcinomas are reliant on androgen receptor (AR) activity for survival and progression. Therefore, first-line therapeutic intervention for disseminated disease entails the use of AR-directed therapeutics, achieved through androgen deprivation and direct AR antagonists. While initially effective, recurrent, 'castrate-resistant' prostate cancers arise, for which there is no durable means of treatment. An abundance of clinical study and preclinical modeling has led to the revelation that restored AR activity is a major driver of therapeutic failure and castrate-resistant prostate cancer development. The mechanisms underpinning AR reactivation have been identified, providing the foundation for a new era of drug discovery and rapid translation into the clinic. As will be reviewed in this article, these creative new ways of suppressing AR show early promise.

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Figures

Figure 1
Figure 1. Mechanisms of androgen receptor reactivation in the transition to castration-resistant prostate cancer
As discussed, tumors evade hormone therapy through restoring AR activity, which can be achieved through multiple mechanisms. Agents designed to target hormone therapy-naive and recurrent AR activity are shown in red. AC: Acetylation; AR: Androgen receptor; CoACT: Coactivator; CoR: Corepressor; CRPC: Castration-resistant prostate cancer; DHT: Dihydrotestosterone; GF: Growth factor; GnRH: Gonadotropin-releasing hormone; HSP: Heat-shock protein; P: Phosphorylation; PSA: Prostate-specific antigen; SNARE: Soluble N-ethylmaleimide-sensitive factor attachment protein receptor; Sumo: Sumolyation; T: Testosterone.
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References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J. Clin. 2009;59:225–249. - PubMed
    1. Singh J, Trabulsi EJ, Gomella LG. Is there an optimal management for localized prostate cancer? Clin. Interv. Aging. 2010;5:187–197. - PMC - PubMed
    1. Grubb RL, Kibel AS. High-risk localized prostate cancer: role of radical prostatectomy. Curr. Opin. Urol. 2010;20:204–210. - PubMed
    1. Garzotto M, Hung AY. Contemporary management of high-risk localized prostate cancer. Curr. Urol. Rep. 2010;11:159–164. - PubMed
    1. Stratton KL, Chang SS. Locally advanced prostate cancer, the role of surgical management. BJU Int. 2009;104:449–454. - PubMed

Website

    1. Clinicaltrials.gov. 2009 Search results for abiraterone http://clinicaltrials.gov/ct2/results?term=abiraterone.