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前列腺类器官方法学、应用及局限性概述。

A synopsis of prostate organoid methodologies, applications, and limitations.

机构信息

Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.

Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, British Columbia, Canada.

出版信息

Prostate. 2020 May;80(6):518-526. doi: 10.1002/pros.23966. Epub 2020 Feb 21.

Abstract

BACKGROUND

Current in vitro modeling systems do not fully reflect the biologic and clinical diversity of prostate cancer (PCa). Organoids are 3D in vitro cell cultures that recapitulate disease heterogeneity, retain prostate gland architecture, and mirror parental tumor characteristics.

METHODS

To make better use of organoid models in the PCa research field, we provide a review of cutting-edge prostate organoid methodologies, applications, and limitations.

RESULTS

We summarize methodologies for the establishment of benign prostate and PCa organoids and describe some of the model's practical applications and challenges. We highlight the patient-derived xenograft (PDX)-organoid interface model, which may allow for the generation of organoids from primary and rare PCa subtypes. Finally, we discuss potential future utilizations of PCa organoids in the realms of drug development and precision oncology.

CONCLUSIONS AND FUTURE DIRECTIONS

Organoids represent a quasi in vivo modeling system that can be easily amenable to genetic modification and functional studies. As such, organoids may serve as an intermediate preclinical model for studying PCa. Future directions may include the refinement of culturing conditions to increase drug response fidelity in PCa organoids. The PDX-organoid interface model may enable the future establishment of primary and rare subtype PCa organoid lines.

摘要

背景

目前的体外建模系统不能完全反映前列腺癌(PCa)的生物学和临床多样性。类器官是 3D 体外细胞培养物,可重现疾病异质性,保留前列腺结构,并反映亲本肿瘤的特征。

方法

为了在 PCa 研究领域更好地利用类器官模型,我们综述了先进的前列腺类器官方法学、应用和局限性。

结果

我们总结了建立良性前列腺和 PCa 类器官的方法,并描述了一些模型的实际应用和挑战。我们强调了患者来源的异种移植(PDX)-类器官界面模型,该模型可能允许从原发性和罕见的 PCa 亚型中生成类器官。最后,我们讨论了 PCa 类器官在药物开发和精准肿瘤学领域的潜在未来应用。

结论和未来方向

类器官代表了一种准体内建模系统,易于进行遗传修饰和功能研究。因此,类器官可以作为研究 PCa 的中间临床前模型。未来的方向可能包括改进培养条件,以提高 PCa 类器官中药物反应的保真度。PDX-类器官界面模型可能能够建立原发性和罕见亚型 PCa 类器官系。

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