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Emerging tumor spheroids technologies for 3D in vitro cancer modeling
Pharmacology & Therapeutics ( IF 13.5 ) Pub Date : 2017-10-31 , DOI: 10.1016/j.pharmthera.2017.10.018
Tânia Rodrigues , Banani Kundu , Joana Silva-Correia , S.C. Kundu , Joaquim M. Oliveira , Rui L. Reis , Vitor M. Correlo

Cancer is a leading cause of mortality and morbidity worldwide. Around 90% of deaths are caused by metastasis and just 10% by primary tumor. The advancement of treatment approaches is not at the same rhythm of the disease; making cancer a focal target of biomedical research. To enhance the understanding and prompts the therapeutic delivery; concepts of tissue engineering are applied in the development of in vitro models that can bridge between 2D cell culture and animal models, mimicking tissue microenvironment. Tumor spheroid represents highly suitable 3D organoid-like framework elucidating the intra and inter cellular signaling of cancer, like that formed in physiological niche. However, spheroids are of limited value in studying critical biological phenomenon such as tumor-stroma interactions involving extra cellular matrix or immune system. Therefore, a compelling need of tailoring spheroid technologies with physiologically relevant biomaterials or in silico models, is ever emerging. The diagnostic and prognostic role of spheroids rearrangements within biomaterials or microfluidic channel is indicative of patient management; particularly for the decision of targeted therapy. Fragmented information on available in vitro spheroid models and lack of critical analysis on transformation aspects of these strategies; pushes the urge to comprehensively overview the recent technological advancements (e.g. bioprinting, micro-fluidic technologies or use of biomaterials to attain the third dimension) in the shed of translationable cancer research. In present article, relationships between current models and their possible exploitation in clinical success is explored with the highlight of existing challenges in defining therapeutic targets and screening of drug efficacy.



中文翻译:

用于3D体外癌症建模的新兴肿瘤球体技术

癌症是全球死亡率和发病率的主要原因。大约90%的死亡是由转移引起的,而只有10%是由原发性肿瘤引起的。治疗方法的进步与疾病的节奏不同。使癌症成为生物医学研究的重点目标。增进了解并促进治疗的进行;组织工程学的概念被应用到体外的发展可以在2D细胞培养和动物模型之间建立桥梁的模型,模仿组织的微环境。肿瘤球体代表高度合适的3D类器官样结构,可阐明癌症的细胞内和细胞间信号传导,就像在生理生态位中形成的一样。然而,球体在研究关键的生物学现象(例如涉及额外细胞基质或免疫系统的肿瘤-基质相互作用)方面的价值有限。因此,迫切需要通过生理相关的生物材料或计算机模型来定制球体技术。生物材料或微流体通道内球体重排的诊断和预后作用指示患者的管理;特别是针对靶向治疗的决策。有关可用的零散信息体外球体模型,并且缺乏对这些策略转化方面的严格分析;推动了在可翻译的癌症研究领域中全面概述最近的技术进步(例如生物打印,微流体技术或使用生物材料以实现三维)的冲动。在本文中,以定义治疗靶点和筛选药效方面的现有挑战为重点,探讨了当前模型与其在临床成功中可能的开发之间的关系。

更新日期:2017-10-31
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