TY - JOUR
T1 - Novel anti-androgen receptor signaling agents
T2 - Understanding the mechanisms of resistance
AU - Karanika, Styliani
AU - Karantanos, Theodoros
AU - Yin, Jianhua
AU - Li, Likun
AU - Thompson, Timothy C.
N1 - Funding Information:
This research is supported in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant, 5 P30 CA16672 , and the Department of Epidemiology, Second Military Medical University, Shanghai, China.
Publisher Copyright:
© 2014 Editorial Office of Asian Journal of Urology.
PY - 2014
Y1 - 2014
N2 - Prostate cancer remains an intractable threat to the lives of men worldwide. Although deaths from prostate cancer (PCA) in the United States have declined in recent years, in other parts of the world Pca mortality is increasing. The introduction of 2nd 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.
AB - Prostate cancer remains an intractable threat to the lives of men worldwide. Although deaths from prostate cancer (PCA) in the United States have declined in recent years, in other parts of the world Pca mortality is increasing. The introduction of 2nd 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.
KW - Anti-androgen receptor agents
KW - Castration-resistant prostate cancer
KW - Combination therapies
KW - Prostate cancer
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U2 - 10.1016/j.ajur.2015.04.004
DO - 10.1016/j.ajur.2015.04.004
M3 - Review article
C2 - 29511635
AN - SCOPUS:85027872389
SN - 2214-3882
VL - 1
SP - 30
EP - 39
JO - Asian Journal of Urology
JF - Asian Journal of Urology
IS - 1
ER -