a Department of Surgery , Medical University of Vienna , Vienna , Austria.
Expert Opin Drug Metab Toxicol. 2019 Jan;15(1):15-23. doi: 10.1080/17425255.2019.1554055. Epub 2018 Dec 2.
: Drug screening assays employing two-dimensional (2D) cultures of cancer cells have been largely replaced by three-dimensional (3D) multicellular tumor spheroid (MCTS) models which more closely represent patient's tumors. The predictive power of the different MCTSs depends on source of the cells, techniques of preparation, and characteristics of the aggregates. : The preparation of MCTSs and a comparison of the spheroids assembled from permanent cancer and patient-derived cell lines in respect to the correlation of their chemosensitivity to clinical responses are discussed. Spheroids formed in in pleural effusion and blood of cancer patients are presented as interesting sources for drug screening. : 3D tumor models for drug screening were adopted to increase the predictive power of assays for success in clinical trials. Cell lines which form dense spheroids differ in physical properties, gene expression, and chemosensitivity from 2D cultures. Still, most of these MCTS models lack characteristics of complex tumor tissues and have not been validated for their adequacy to select clinically useful drugs. Patient-derived spheroids from pleural effusion or blood, namely tumorospheres of circulating tumor cells, are MCTS models most similar to patient's tumors.
: 采用二维(2D)培养的癌细胞药物筛选测定法已被三维(3D)多细胞肿瘤球体(MCTS)模型所取代,后者更能代表患者的肿瘤。不同 MCTS 的预测能力取决于细胞的来源、制备技术和聚集体的特征。 : 讨论了 MCTS 的制备以及从永久性癌症和患者来源的细胞系中组装的球体在其对临床反应的化学敏感性的相关性方面的比较。来自癌症患者胸腔积液和血液中的球体被提出作为药物筛选的有趣来源。 : 为了提高临床试验成功的测定法的预测能力,已经采用 3D 肿瘤模型进行药物筛选。形成密集球体的细胞系在物理性质、基因表达和化学敏感性方面与 2D 培养物不同。尽管如此,这些 MCTS 模型中的大多数缺乏复杂肿瘤组织的特征,并且尚未对其选择临床有用药物的充分性进行验证。来自胸腔积液或血液的患者来源的球体,即循环肿瘤细胞的肿瘤球体,是与患者肿瘤最相似的 MCTS 模型。