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患者来源模型系统与下一代抗癌治疗药物的研发。

Patient-derived model systems and the development of next-generation anticancer therapeutics.

机构信息

Allcyte GmbH, 1030, Vienna, Austria.

CeMM Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.

出版信息

Curr Opin Chem Biol. 2020 Jun;56:72-78. doi: 10.1016/j.cbpa.2020.01.002. Epub 2020 Feb 18.

DOI:10.1016/j.cbpa.2020.01.002
PMID:32086157
Abstract

Anticancer drug discovery and development using conventional cell line and animal models has traditionally had a low overall success rate. Despite yielding game-changing new therapeutics, 10-20 new molecules have to be brought to the clinic to obtain one new approval, making this approach costly and inefficient. The use of in vitro experimental models based on primary human tumour tissues has the potential to provide a representation of human cancer biology that is closer to an actual patient and to 'bridge the translational gap' between preclinical and clinical research. Here, we review recent advances in the use of human tumour samples for preclinical research through organoid development or as primary patient materials. While challenges still remain regarding analysis, validation and scalability, evidence is mounting for the applicability of both models as preclinical research tools.

摘要

传统的细胞系和动物模型在抗癌药物的发现和开发方面整体成功率一直较低。尽管取得了改变游戏规则的新疗法,但仍需要将 10-20 种新分子推向临床,才能获得一项新的批准,这使得这种方法成本高昂且效率低下。使用基于人原发性肿瘤组织的体外实验模型有可能提供更接近实际患者的人类癌症生物学的代表性,并“弥合临床前和临床研究之间的转化差距”。在这里,我们回顾了最近在通过类器官开发或作为原发性患者材料使用人类肿瘤样本进行临床前研究方面的进展。虽然在分析、验证和可扩展性方面仍然存在挑战,但越来越多的证据表明这两种模型都可以作为临床前研究工具。

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