Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer.
Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer.
复制标题
恩扎拉胺：靶向转移性cast割前列腺癌中的雄激素信号通路。
DOI：
10.1111/bju.13123
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发表时间：
2016-02
影响因子：
4.5
通讯作者：
Fitzpatrick JM
中科院分区：
文献类型：
--
作者：
Schalken J;Fitzpatrick JM
在对去势抵抗性前列腺癌（CRPC）的潜在癌症生物学的理解方面取得了重大进展，其中雄激素受体（AR）信号通路仍然涉及整个前列腺癌疾病连续体。AR信号通路的重新激活被认为是CRPC进展的关键驱动因素，因此，AR是CRPC治疗的合理靶点。本综述的目的是了解AR信号传导在治疗转移性CRPC（mCRPC）患者中的重要性，并讨论与抑制AR信号传导通路相关的临床获益。进行检索以识别与AR信号传导在CRPC中的作用和抑制AR信号传导途径的治疗相关的文章。目前对前列腺癌的理解已经将AR信号通路确定为治疗CRPC的逻辑靶点。抑制AR信号传导途径的可用疗法包括AR阻断剂、雄激素生物合成抑制剂和AR信号传导抑制剂。Enzalutamide是首个获批的AR信号传导抑制剂，具有靶向三个关键阶段AR信号传导的新型作用模式。Enzalutamide的直接作用模式已被证明可转化为mCRPC患者的临床应答。总之，在mCRPC患者中靶向AR信号通路可产生许多临床获益。随着治疗选择的增加，需要更多的试验来评估治疗的顺序和组合。本综述强调了针对CRPC进展中的关键驱动因素AR信号传导的持续重要性，以及与抑制AR信号传导通路治疗CRPC患者相关的临床获益。
Significant progress has been made in the understanding of the underlying cancer biology of castration‐resistant prostate cancer (CRPC) with the androgen receptor (AR) signalling pathway remaining implicated throughout the prostate cancer disease continuum. Reactivation of the AR signalling pathway is considered to be a key driver of CRPC progression and, as such, the AR is a logical target for therapy in CRPC. The objective of this review was to understand the importance of AR signalling in the treatment of patients with metastatic CRPC (mCRPC) and to discuss the clinical benefits associated with inhibition of the AR signalling pathway. A search was conducted to identify articles relating to the role of AR signalling in CRPC and therapies that inhibit the AR signalling pathway. Current understanding of prostate cancer has identified the AR signalling pathway as a logical target for the treatment of CRPC. Available therapies that inhibit the AR signalling pathway include AR blockers, androgen biosynthesis inhibitors, and AR signalling inhibitors. Enzalutamide, the first approved AR signalling inhibitor, has a novel mode of action targeting AR signalling at three key stages. The direct mode of action of enzalutamide has been shown to translate into clinical responses in patients with mCRPC. In conclusion, the targeting of the AR signalling pathway in patients with mCRPC results in numerous clinical benefits. As the number of treatment options increase, more trials evaluating the sequencing and combination of treatments are required. This review highlights the continued importance of targeting a key driver in the progression of CRPC, AR signalling, and the clinical benefits associated with inhibition of the AR signalling pathway in the treatment of patients with CRPC.