Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Paul O'Gorman building, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Department of Urology, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
Int J Mol Sci. 2020 Jan 30;21(3):905. doi: 10.3390/ijms21030905.
One of the key issues hampering the development of effective treatments for prostate cancer is the lack of suitable, tractable, and patient-specific in vitro models that accurately recapitulate this disease. In this review, we address the challenges of using primary cultures and patient-derived xenografts to study prostate cancer. We describe emerging approaches using primary prostate epithelial cells and prostate organoids and their genetic manipulation for disease modelling. Furthermore, the use of human prostate-derived induced pluripotent stem cells (iPSCs) is highlighted as a promising complimentary approach. Finally, we discuss the manipulation of iPSCs to generate 'avatars' for drug disease testing. Specifically, we describe how a conceptual advance through the creation of living biobanks of "genetically engineered cancers" that contain patient-specific driver mutations hold promise for personalised medicine.
阻碍开发有效前列腺癌治疗方法的一个关键问题是缺乏合适的、易于处理的和患者特异性的体外模型,这些模型能够准确地再现这种疾病。在这篇综述中,我们讨论了使用原代培养物和患者来源的异种移植物研究前列腺癌所面临的挑战。我们描述了使用原代前列腺上皮细胞和前列腺类器官及其遗传操作进行疾病建模的新方法。此外,还强调了使用人前列腺衍生的诱导多能干细胞(iPSCs)作为一种有前途的互补方法。最后,我们讨论了操纵 iPSCs 以生成用于药物疾病测试的“化身”。具体来说,我们描述了通过创建包含患者特异性驱动突变的“基因工程癌症”的活体生物库这一概念上的进展如何为个性化医疗带来希望。