Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer.
Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer.
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DOI：
10.7150/ijbs.14090
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发表时间：
2016
影响因子：
9.2
通讯作者：
Koochekpour S
中科院分区：
文献类型：
--
作者：
Wadosky KM;Koochekpour S
局限性前列腺癌（PCa）患者有几种预后良好的治疗选择。然而，高风险晚期前列腺癌患者的生存率明显低于早期器官受限疾病患者。自1941年以来，睾酮和其他雄激素与前列腺癌的进展直接相关。在这篇综述中，我们记录了导致PCa现代治疗策略的发现。特别强调的是雄激素受体（AR）的生物学，这是一种核受体转录因子，主要负责雄激素刺激和去势复发（CR） PCa。目前的前列腺癌治疗范式可分为三种不同但相互关联的类别：靶向受体前、受体或受体后信号。疾病复发的持续挑战作为CR和/或转移性肿瘤，注定发生在初始治疗的三年内，也进行了讨论。我们的结论是，未来PCa治疗的成功取决于靶向肿瘤复发的分子机制，这些机制仍然可能在受体前、受体和受体后水平上影响AR。
Patients with localized prostate cancer (PCa) have several therapeutic options with good prognosis. However, survival of patients with high-risk, advanced PCa is significantly less than patients with early-stage, organ-confined disease. Testosterone and other androgens have been directly linked to PCa progression since 1941. In this review, we chronicle the discoveries that led to modern therapeutic strategies for PCa. Specifically highlighted is the biology of androgen receptor (AR), the nuclear receptor transcription factor largely responsible for androgen-stimulated and castrate-recurrent (CR) PCa. Current PCa treatment paradigms can be classified into three distinct but interrelated categories: targeting AR at pre-receptor, receptor, or post-receptor signaling. The continuing challenge of disease relapse as CR and/or metastatic tumors, destined to occur within three years of the initial treatment, is also discussed. We conclude that the success of PCa therapies in the future depends on targeting molecular mechanisms underlying tumor recurrence that still may affect AR at pre-receptor, receptor, and post-receptor levels.