Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Drug Discov Today. 2018 Oct;23(10):1776-1783. doi: 10.1016/j.drudis.2018.05.015. Epub 2018 May 24.
Next-generation sequencing (NGS) enabled high-throughput analysis of genotype-phenotype relationships on human populations, ushering in a new era of genetics-informed drug development. The year 2017 was remarkable, with the first FDA-approved gene therapy for cancer (Kymriah™) and for inherited diseases (LUXTURNA™), the first multiplex NGS panel for companion diagnostics (MSK-IMPACT™) and the first drug targeting a genetic signature rather than a disease (Keytruda). We envision that population-scale NGS with paired electronic health records (EHRs) will become a routine measure in the drug development process for the identification of novel drug targets, and that genetically stratified clinical trials could be widely adopted to improve power in precision-medicine-guided drug development.
下一代测序（NGS）实现了对人类群体的基因型-表型关系进行高通量分析，开创了遗传学指导药物开发的新时代。2017 年是不平凡的一年，FDA 批准了首个用于癌症（Kymriah™）和遗传性疾病（LUXTURNA™）的基因治疗药物，首个用于伴随诊断的多重 NGS 检测 panel（MSK-IMPACT™），以及首个针对遗传特征而非疾病的药物（Keytruda）。我们设想，结合电子健康记录（EHRs）的人群规模 NGS 将成为药物开发过程中识别新型药物靶点的常规手段，而基于基因分层的临床试验可能会被广泛采用，以提高精准医学指导药物开发的效能。
