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

作　　者：Styliani Karanika Theodoros Karantanos Jianhua Yin Likun Li Timothy C.Thompson 

机构地区：[1]Department of Genitourinary Medical Oncology,The University of Texas MD Anderson Cancer Center,Houston,TX,USA [2]Department of Epidemiology,Second Military Medical University,Shanghai,China

出　　处：《Asian Journal of Urology》2014年第1期30-39,共10页亚洲泌尿外科杂志（英文）

基　　金：supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant,5 P30 CA16672;the Department of Epidemiology,Second Military Medical University,Shanghai,China.

摘　　要：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 antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant 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.

关 键 词：Prostate cancer Castration-resistant prostate cancer Anti-androgen receptor agents Combination therapies 

分 类 号：R58[医药卫生—内分泌]