Kato Manabu, Sasaki Takeshi, Inoue Takahiro
Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Int J Urol. 2021 Feb;28(2):150-162. doi: 10.1111/iju.14441. Epub 2020 Nov 27.
Scientists engaged in prostate cancer research have been conducting experiments using two-dimensional cultures of prostate cancer cell lines for decades. However, these experiments fail to reproduce and reflect the clinical course of individual patients with prostate cancer, or the molecular and genetic characteristics of prostate cancer, the basic requirement for most of the preclinical studies on prostate cancer. The use of human prostate cancer tissues in experiments has enabled the collection and verification of clinically relevant data, including chemical reactions, changes in proteins, and specific gene expression. Tissue recombination models have been employed for studying prostate development, the initiation and progression of prostate cancer, and the tumor microenvironment. Notably, the epithelial-stromal interaction, which might play a critical role in prostate cancer pathogenesis, can be reproduced in this model. Patient-derived xenograft models have been developed as powerful avatars comprising patient-derived prostate cancer tissues implanted in immunocompromised mice and could serve as a precision medicine approach for each prostate cancer patient. Spheroid and organoid assays, representative of modern three-dimensional cultures, can replicate the conditions in human prostate tumors and the prostate organ itself as a miniature model. Although an intact immune system against the tumor is missing from the models aimed at investigating immuno-oncological reagents in various malignancies, all these experimental models can help researchers in developing new drugs and selecting appropriate treatment strategies for prostate cancer patients.
几十年来，从事前列腺癌研究的科学家们一直在使用前列腺癌细胞系的二维培养物进行实验。然而，这些实验无法重现和反映前列腺癌个体患者的临床病程，也无法反映前列腺癌的分子和遗传特征，而这是大多数前列腺癌临床前研究的基本要求。在实验中使用人类前列腺癌组织能够收集和验证临床相关数据，包括化学反应、蛋白质变化和特定基因表达。组织重组模型已被用于研究前列腺发育、前列腺癌的发生和发展以及肿瘤微环境。值得注意的是，上皮-基质相互作用可能在前列腺癌发病机制中起关键作用，这种相互作用可以在该模型中重现。患者来源的异种移植模型已被开发出来，作为一种强大的模型，它由植入免疫缺陷小鼠体内的患者来源的前列腺癌组织组成，可作为针对每位前列腺癌患者的精准医疗方法。作为现代三维培养的代表，球体和类器官检测可以作为微型模型重现人类前列腺肿瘤和前列腺器官本身的条件。尽管旨在研究各种恶性肿瘤免疫肿瘤学试剂的模型缺乏针对肿瘤的完整免疫系统，但所有这些实验模型都可以帮助研究人员开发新药，并为前列腺癌患者选择合适的治疗策略。
