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人类前列腺癌异种移植的内容、时间及原因

The what, when, and why of human prostate cancer xenografts.

作者信息

Brennen W Nathaniel, Isaacs John T

机构信息

Department of Oncology, Prostate Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

出版信息

Prostate. 2018 Jun;78(9):646-654. doi: 10.1002/pros.23510. Epub 2018 Mar 24.

Abstract

BACKGROUND

Presently, ∼85 serially transplantable human prostate cancer xenografts spanning the phenotypic, epigenetic, and genetic heterogeneity seen clinically are available in a variety of laboratories throughout the world. If distributed to the prostate cancer research community, these can provide an experimental platform for resolving the specificity versus generalizability of basic cancer biology principles (eg, credentialing of therapeutic molecular targets) and for validating translational approaches for prevention, diagnosis, and therapy. Thus, there is an urgent need to distribute the already established serially transplantable human prostate cancer xenografts and to develop robust methods for establishing new ones.

METHODS

To accelerate the development of such additional xenografts, particularly from patients treated with the newer standard of care agents (ie, abiraterone, enzalutamide, cabazitaxel, alpharadin, etc), a historic review of the field will be presented.

RESULTS

Over the last 50 years, multiple groups throughout the world have developed methods for the successful establishment of serially transplantable human prostate cancer xenografts using a variety of immune deficient mice. These are summarized chronologically.

CONCLUSIONS AND FUTURE

With the ever growing appreciation of the value of personalized medicine (aka precision medicine), methods need to be developed that allow efficient and timely growth of primary patient derived prostate cancer xenografts (PDXs), which can be used as "avatars" for defining optimal therapy for that specific patient. Such development should be based upon the leads obtained from the successful establishment of serially transplantable prostate cancer xenografts described in this review.

摘要

背景

目前,世界各地的多个实验室拥有约85种可连续传代移植的人类前列腺癌异种移植模型,这些模型涵盖了临床上所见的表型、表观遗传和基因异质性。如果将这些模型分发给前列腺癌研究群体,它们可为解决基础癌症生物学原理的特异性与普遍性问题(例如,验证治疗分子靶点)以及验证预防、诊断和治疗的转化方法提供实验平台。因此,迫切需要分发已建立的可连续传代移植的人类前列腺癌异种移植模型,并开发建立新模型的可靠方法。

方法

为了加速此类额外异种移植模型的开发,特别是来自接受更新的标准治疗药物(即阿比特龙、恩杂鲁胺、卡巴他赛、α粒子放疗等)治疗的患者的模型,将对该领域进行历史性回顾。

结果

在过去50年中,世界各地的多个团队开发了多种方法,利用各种免疫缺陷小鼠成功建立了可连续传代移植的人类前列腺癌异种移植模型。现将这些方法按时间顺序进行总结。

结论与未来展望

随着人们对个性化医疗(又称精准医疗)价值的认识不断提高,需要开发能够高效、及时地培养原发性患者来源的前列腺癌异种移植模型(PDX)的方法,这些模型可作为“化身”来确定针对该特定患者的最佳治疗方案。这种开发应基于本综述中成功建立可连续传代移植的前列腺癌异种移植模型所获得的经验。

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