Düsseldorf, Germany.
Drug Discov Today. 2017 Nov;22(11):1598-1603. doi: 10.1016/j.drudis.2017.04.019. Epub 2017 May 22.
The pharmaceutical industry is tackling increasingly complex multifactorial diseases, resulting in increases in research & development (R&D) costs and reductions in the success rates for drug candidates during Phase 2 and 3 clinical trials, with a lack of efficacy being the primary reason for drug candidate failure. This implies that the predictive power of current preclinical assays for drug candidate efficacy is suboptimal and, therefore, that alternatives should be developed. Here, I review emerging in vitro, imaging, and in silico technologies and discuss their potential contribution to drug efficacy assessment. Importantly, these technologies are complimentary and can be bundled into the preclinical platform. In particular, patient-on-a-chip recapitulates both human genetics and physiology. The response of a patient-on-a-chip to drug candidate treatment is monitored with light-sheet fluorescent microscopy and fed into the image-analysis pipeline to reconstruct an image-based systems-level model for disease pathophysiology and drug candidate mode of action. Thus, such models could be useful tools for assessing drug candidate efficacy and safety in humans.
制药行业正在应对日益复杂的多因素疾病，导致研究与开发（R&D）成本增加，以及在第 2 阶段和第 3 阶段临床试验中候选药物的成功率降低，候选药物疗效不佳是导致候选药物失败的主要原因。这意味着目前候选药物疗效的临床前检测的预测能力还不够理想，因此应该开发替代方法。在这里，我回顾了新兴的体外、成像和计算机技术，并讨论了它们在药物疗效评估方面的潜在贡献。重要的是，这些技术是互补的，可以组合到临床前平台中。特别是，芯片上的患者可以重现人类遗传学和生理学。使用光片荧光显微镜监测芯片上的患者对候选药物治疗的反应，并将其输入图像分析管道，以重建基于图像的系统级疾病病理生理学和候选药物作用模式的模型。因此，这些模型可能是评估候选药物在人体中的疗效和安全性的有用工具。
