Heath James R, Ribas Antoni, Mischel Paul S
California Institute of Technology Division of Chemistry and Chemical Engineering, MC 127-72, 1200 East California Boulevard, Pasadena, California 91125, USA.
Department of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
Nat Rev Drug Discov. 2016 Mar;15(3):204-16. doi: 10.1038/nrd.2015.16. Epub 2015 Dec 16.
The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed.
健康组织和患病组织在基因、功能或组成上的异质性给药物研发带来了重大挑战。这种异质性阻碍了精确疾病模型的设计,可能混淆生物标志物水平以及患者对特定疗法反应的解读。几乎所有组织的复杂特性推动了单细胞基因组、转录组和多重蛋白质组分析工具的发展。在此,我们回顾这些工具并评估其优缺点。还将讨论单细胞分析工具在药物研发,尤其是肿瘤学领域的新兴应用。