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精准医学时代晚期前列腺癌的雌激素和雄激素阻断治疗

Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine.

作者信息

Fujimura Tetsuya, Takayama Kenichi, Takahashi Satoru, Inoue Satoshi

机构信息

Department of Urology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.

Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.

出版信息

Cancers (Basel). 2018 Jan 23;10(2):29. doi: 10.3390/cancers10020029.

Abstract

Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually acquires a lethal phenotype and results in castration-resistant PC (CRPC) during ADT. Therefore, new therapeutic strategies are required in clinical practice. In addition, ARs; estrogen receptors (ERs; ERα and ERβ); and estrogen-related receptors (ERRs; ERRα, ERRβ, and ERRγ) have been reported to be involved in the development or regulation of PC. Recent investigations have revealed the role of associated molecules, such as , , , , , , and of PC, via ERs and ERRs. Selective ER modulators (SERMs) have been developed. Recently, estrogen and androgen blockade (EAB) using a combination of toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC. In the future, the suitability of ADT alone or EAB for individuals may be evaluated by making clinical decisions on the basis of information obtained from RT-PCR, gene-panel, or liquid biopsy to create a "personalized medicine" or "precision medicine". In this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and SERMs as candidates for advanced PC treatment.

摘要

雄激素剥夺疗法(ADT)已被广泛应用于晚期前列腺癌(PC)患者,以通过雄激素受体(AR)和AR协作转录因子控制关键信号通路;然而,在ADT期间,PC会逐渐获得致命表型,并导致去势抵抗性PC(CRPC)。因此,临床实践中需要新的治疗策略。此外,据报道,AR、雌激素受体(ERs;ERα和ERβ)以及雌激素相关受体(ERRs;ERRα、ERRβ和ERRγ)参与了PC的发生发展或调控。最近的研究揭示了相关分子,如PC的 、 、 、 、 、 和 通过ERs和ERRs所起的作用。选择性ER调节剂(SERM)已被开发出来。最近,已证明使用托瑞米芬和ADT联合进行雌激素和雄激素阻断(EAB)可提高初治骨转移性PC的生化复发率。未来,可根据从RT-PCR、基因检测板或液体活检获得的信息做出临床决策,以评估单独使用ADT或EAB对个体的适用性,从而创建“个性化医疗”或“精准医疗”。在本综述中,我们总结了ER和ERR信号通路、分子诊断以及作为晚期PC治疗候选药物的SERM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e8e/5836061/9489e2d9a2c2/cancers-10-00029-g001.jpg

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