文章：

去势抵抗性与高剂量睾酮抵抗性前列腺癌细胞模型重现了临床实践中观察到的反应异质性

Cell Models of Castration Resistant and High Dose Testosterone-Resistant Prostate Cancer Recapitulate the Heterogeneity of Response Observed in Clinical Practice

原文发布日期：10 February 2025

DOI: 10.3390/cancers17040593

类型: Article

开放获取: 是

英文摘要：

The use of supraphysiologic testosterone, particularly when alternated with an anti-androgen agent in men with metastatic castration-resistant prostate cancer (CRPC), has demonstrated promising results in clinical trials. As the use of this therapy in clinical practice is more widely adopted, there will be a growing need to understand the mechanisms of resistance. To that end, we independently derived three separate cell models of testosterone-sensitive CRPC. From each CRPC line, high dose testosterone-resistance (HTR) lines were selected. We demonstrated the differential response of the three CRPC lines to a high dose of testosterone in vitro and in vivo. We subsequently demonstrated the resistance of the HTR lines to testosterone and varying responses to testosterone withdrawal in vivo. The heterogeneity in responses to hormonal manipulation is correlated with varying levels of androgen receptor expression within the population. Overall, we show that we have developed three models of HTR that can be used to study the mechanisms of high dose testosterone resistance and identify potential therapeutic targets.

摘要翻译： 

在转移性去势抵抗性前列腺癌（CRPC）患者中，使用超生理剂量睾酮，特别是与抗雄激素药物交替使用的疗法，已在临床试验中显示出令人鼓舞的结果。随着该疗法在临床实践中的应用日益广泛，理解其耐药机制的需求也日益增长。为此，我们独立构建了三种不同的睾酮敏感性CRPC细胞模型。从每种CRPC细胞系中，我们筛选出了高剂量睾酮耐药（HTR）细胞系。我们证明了这三种CRPC细胞系在体外和体内对高剂量睾酮的不同反应。随后，我们证实了HTR细胞系对睾酮的耐药性，以及在体内对睾酮撤除的不同反应。这种对激素干预反应的异质性与细胞群体内雄激素受体表达水平的差异相关。总体而言，我们成功建立了三种HTR模型，可用于研究高剂量睾酮耐药的机制，并识别潜在的治疗靶点。

原文链接：

Cell Models of Castration Resistant and High Dose Testosterone-Resistant Prostate Cancer Recapitulate the Heterogeneity of Response Observed in Clinical Practice