Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged H-6726, Hungary; and at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
European Cell-Based Assays Interest Group.
Nat Rev Drug Discov. 2016 Nov;15(11):751-769. doi: 10.1038/nrd.2016.175. Epub 2016 Sep 12.
The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell- and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates.
将有前景的临床前药物候选物转化为临床成功的常见且持续的失败，突显了当前用于药物发现的疾病模型的有限有效性。人们显然不愿意探索和采用替代的基于细胞和组织的模型系统，并且在测定验证过程中与临床实践脱节，这导致转化研究效果不佳。为了帮助解决这些问题并引发讨论，我们在这里提出了一系列原则，以促进相关疾病测定的定义和发展，并且我们讨论了在药物发现中利用基于细胞的测定技术最新进展的新机会，包括诱导多能干细胞、三维（3D）共培养和器官芯片系统，同时结合单细胞成像和基因编辑技术的进步。为支持开展具有竞争力的多学科合作以开发新型临床前模型和基于细胞的筛选技术提供资金，可能对提高其临床相关性并最终提高临床成功率发挥关键作用。
