Novel anti-androgen receptor signaling agents: understanding the mechanisms of resistance

Asian Journal of Urology, 2014, 1 (1): 28-37 doi:

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Novel anti-androgen receptor signaling agents: understanding the mechanisms of resistance

Styliani Karanika¹, Theodoros Karantanos¹, Jianhua Yin^1,2, Likun Li¹, Timothy C. Thompson¹

1. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
2. Department of Epidemiology, Second Military Medical University, Shanghai, China

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Abstract Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer in the United States have declined in recent years, in other parts of the world prostate cancer mortality is increasing.The introduction of 2^nd generation anti-androgen receptor agents into the therapeutic armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has resulted in modestly increased survival advantages as demonstrated by initial clinical trials.However, analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mCRPC, including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen signaling.Combination therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of mCRPC.In this review, we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and enzalutamide.We discuss observational data that point to mechanisms of resistance that emerged from these studies.We further present and discuss recent experimental studies that address the mechanisms of resistance to these treatments.Finally, we discuss novel and rational therapeutic approaches, including combination therapy, for patients with mCRPC.

Key words： Prostate cancer Castration-resistant prostate cancer Anti-androgen receptor agents Combination therapies

Received: 02 August 2014 Published: 28 October 2014

Corresponding Authors: Timothy C. Thompson E-mail: timthomp@mdanderson.org

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Styliani Karanika,Theodoros Karantanos,Jianhua Yin, et al. Novel anti-androgen receptor signaling agents: understanding the mechanisms of resistance[J]. Asian Journal of Urology, 2014, 1(1): 28-37.

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http://www.ajurology.com/EN/ OR http://www.ajurology.com/EN/Y2014/V1/I1/28

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