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Int J Biol Sci 2016; 12(4):409-426. doi:10.7150/ijbs.14090

Review

Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer

Kristine M Wadosky, Shahriar Koochekpour

Departments of Cancer Genetics and Urology, Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, USA.

Abstract

Patients with localized prostate cancer (PCa) have several therapeutic options with good prognosis. However, survival of patients with high-risk, advanced PCa is significantly less than patients with early-stage, organ-confined disease. Testosterone and other androgens have been directly linked to PCa progression since 1941. In this review, we chronicle the discoveries that led to modern therapeutic strategies for PCa. Specifically highlighted is the biology of androgen receptor (AR), the nuclear receptor transcription factor largely responsible for androgen-stimulated and castrate-recurrent (CR) PCa. Current PCa treatment paradigms can be classified into three distinct but interrelated categories: targeting AR at pre-receptor, receptor, or post-receptor signaling. The continuing challenge of disease relapse as CR and/or metastatic tumors, destined to occur within three years of the initial treatment, is also discussed. We conclude that the success of PCa therapies in the future depends on targeting molecular mechanisms underlying tumor recurrence that still may affect AR at pre-receptor, receptor, and post-receptor levels.

Keywords: Prostate cancer, androgen, AR, castrate-recurrent, treatment, FDA.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wadosky KM, Koochekpour S. Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer. Int J Biol Sci 2016; 12(4):409-426. doi:10.7150/ijbs.14090. Available from http://www.ijbs.com/v12p0409.htm