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.
前列腺癌是男性常见癌症，通常进展缓慢，历经数十年才发展为侵袭性肿瘤并转移至其他器官，此时治疗选择极为有限。尽管已有大型动物研究，但犬类前列腺在解剖结构上与人类相似，曾被用于研究自发性前列腺癌。然而，目前大多数研究以小鼠作为模式生物，因其前列腺组织可通过基因修饰进行分子分析。该研究领域的重要里程碑之一是前列腺特异性启动子Probasin的发现，该启动子实现了转基因在前列腺的特异性表达。通过过表达SV40癌基因，研究人员成功构建了具有侵袭性前列腺肿瘤的小鼠模型。Probasin启动子还可用于驱动Cre重组酶表达，使前列腺特异性功能缺失研究成为可能。小鼠前列腺癌建模进程中的另一标志性进展是病毒颗粒的正交递送技术。该技术通过慢病毒选择性过表达癌基因，或利用CRISPR技术开展复杂的功能缺失研究。这些基因修饰模型与免疫缺陷小鼠中经典的人类前列腺肿瘤细胞异种移植模型形成互补。总体而言，临床前模型已构建出系列研究体系，用于探索前列腺癌的复杂机制并拓展治疗策略。本综述将重点阐述各项技术的研究进展。
肿瘤(癌症)患者之家