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雄激素受体阻塞及其对前列腺癌PSMA局部化的影响:对放射性体疗法的影响

Flavien Devaux¹, Kareem Beltagi¹, Thomas Frank Ermler¹

¹Department of Urology and Pediatric Urology, University Hospital RWTH Aachen, Aachen, Germany; Center for Integrated Oncology (CIO), University Hospital RWTH Aachen, Aachen, Germany.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|December 3, 2025

概括

抗雄激素受体阻塞通过增加PSMA膜局部化来增强前列腺癌放射性体疗法. 然而,过度封锁会导致ER压力,减少PSMA吸收,需要个性化治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
放射化学放射化学是指辐射化学.

背景情况:

前列腺特异性膜抗原 (PSMA) 是前列腺癌 (PCa) 放射性连接体疗法 (RLT) 的关键标.
PSMA的亚细胞局部化通过通过PSMA介导的内细胞分裂通过连接体的吸收显著影响RLT的疗效.
雄激素受体阻断 (ARB) 是一种标准的PCa治疗方法,但其对PSMA贩运的影响尚未完全理解.

研究的目的:

调查ARB对PSMA膜贩运PCa的影响.
为了确定细胞内膜网膜 (ER) 应激是否调节ARB对PSMA局部化的影响.
评估优化ARB和RLT的联合疗效.

主要方法:

在PCa细胞系 (LNCaP,VCaP) 接受了不同剂量和持续时间的恩扎胺 (ARB) 治疗.
评估PSMA局部使用光学切割,光定位和西方涂抹.
量化了ER压力标志物 (BiP,PERK),[177Lu]Lu-PSMA-I&T摄入量以及治疗疗效 (MTS,活/死染色).

主要成果:

ARB显著增加了PSMA膜局部化,在体外增强了[177Lu]Lu-PSMA-I&T的吸收.
长时间或高剂量的ARB诱导了ER压力,导致PSMA贩运减少和放射性体吸收减少.
优化的ARB-RLT组合显示显著增强治疗疗效.

结论:

通过优化前列腺癌中的PSMA膜局部化,ARB可以提高RLT的效率.
ER压力作为监测PSMA贩运和指导个性化ARB调整的潜在生物标志物.
进一步验证ER压力标志物对于开发个性化的ARB-RLT策略以改善临床结果至关重要.

关键词:

这是一种安德罗基因.膜膜是一种膜.在PSMA上,PSMA可以在PSMA上进行交易.前列腺前列腺前列腺无线电连接物和无线电连接物.

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