研究动态
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前临床模型研究人类前列腺癌。

Pre-Clinical Models to Study Human Prostate Cancer.

发表日期:2023 Aug 22
作者: Martin K Thomsen, Morten Busk
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

前列腺癌是男性常见的癌症,通常在数十年之后才会发展为恶性并蔓延到其他器官,治疗选择有限。虽然已经研究了大型动物,但狗的前列腺在解剖上与人类相似,并且已被用于研究自发性前列腺癌。然而,目前大部分研究都集中在老鼠这个模式生物上,因为可以对它们的前列腺组织进行基因修饰以进行分子分析。在这项研究中的一个里程碑是前列腺特异性启动子Probasin的发现,它使转基因的前列腺特异性表达成为可能。这导致了通过SV40致癌基因的过度表达在小鼠中生成了具有侵袭性的前列腺肿瘤。Probasin启动子还被用于驱动Cre的表达,使研究人员能够进行前列腺特异性的功能缺失研究。在模拟小鼠前列腺癌过程中的另一个重要时刻是正交传送病毒颗粒。这项技术允许从慢病毒中选择性地过度表达致癌基因,或使用CRISPR构建复杂的功能缺失研究。这些基因修饰的模型与免疫缺陷小鼠中的人类前列腺肿瘤细胞的经典异种移植相结合。总的来说,临床前模型为研究和解决前列腺癌中复杂机制提供了一系列模型系统,以寻求改进的治疗选择。本综述将着重介绍每种技术的进展。
Prostate cancer is a common cancer among men and typically progresses slowly for several decades before becoming aggressive and spreading to other organs, leaving few treatment options. While large animals have been studied, the dog's prostate is anatomically similar to humans and has been used to study spontaneous prostate cancer. However, most research currently focuses on the mouse as a model organism due to the ability to genetically modify their prostatic tissues for molecular analysis. One milestone in this research was the identification of the prostate-specific promoter Probasin, which allowed for the prostate-specific expression of transgenes. This has led to the generation of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and has allowed researchers to generate prostate-specific loss-of-function studies. Another landmark moment in the process of modeling prostate cancer in mice was the orthoptic delivery of viral particles. This technology allows the selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss-of-function studies. These genetically modified models are complemented by classical xenografts of human prostate tumor cells in immune-deficient mice. Overall, pre-clinical models have provided a portfolio of model systems to study and address complex mechanisms in prostate cancer for improved treatment options. This review will focus on the advances in each technique.