The androgen/androgen receptor axis in prostate cancer.
The androgen/androgen receptor axis in prostate cancer.
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DOI：
10.1097/cco.0b013e32835105b3
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发表时间：
2012-05
影响因子：
3.4
通讯作者：
Nelson PS
中科院分区：
文献类型：
--
作者：
Bluemn EG;Nelson PS
这篇综述强调了最近发现的维持去势抵抗性前列腺癌（CRPC）生长的机制，并描述了CRPC治疗的进展。最近的报道揭示了CRPC在雄激素剥夺治疗（ADT）期间生存的分子过程。本报告总结了最近的研究结果，并对其临床相关性进行了评论。包括在这篇评论是一个讨论的分子机制，调节AR信号在正常前列腺上皮细胞和CRPC，雄激素依赖性（AD）前列腺癌和CRPC的雄激素调节的转录程序的生物学显着差异，以及最近的发现涉及从头雄激素的生产和运输。我们回顾了目前的临床试验的状态和结果，最后，讨论了证据表明AR信号在前列腺癌中的重要性下降与PTEN损失的影响。对CRPC中AR信号传导的理解的进展已经确定了新的药物靶点，并改进了靶向治疗的合理设计，同时阐明了可能进展为完全独立于AR信号传导程序的前列腺癌子集。
This review highlights recently discovered mechanisms that sustain castration-resistant prostate cancer (CRPC) growth and describes advances in CRPC therapeutics. Recent reports have shed new light on the molecular processes underlying CRPC survival during androgen deprivation therapy (ADT). This report summarizes recent findings and comments on their clinical relevance. Included in this review is a discussion on molecular mechanisms that regulate AR signaling in normal prostate epithelium and CRPC, biologically significant differences in the androgen-regulated transcriptional programs of androgen-dependent (AD) prostate cancer and CRPC, and recent discoveries involving de novo androgen production and transport. We review the status and results of current clinical trials and finally, discuss the implications of evidence suggesting a declining importance of AR-signaling in prostate cancers with PTEN loss. Advances in the understanding of AR signaling in CRPC have identified novel drug targets and improved the rational design of targeted therapy, while illuminating a subset of prostate cancers that may progress to become completely independent of the AR signaling program.