Reimagining human-centric drug development with new approach methodologies

• 成果类型: Review
• 署名作者: Wu, Xuekun; Wu, Matthew A.; Zou, James; Kleinstreuer, Nicole; Wu, Joseph C.
• 署名单位: Stanford Medicine; Stanford University; Stanford Medicine; Stanford University; Stanford University; National Institutes of Health (NIH) - USA
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aeb0045
• 发表日期: 2026-04-23
• 页码: 371-378
• 关键词: pluripotent stem-cells; clinical-trial; ORGANOID BIOBANK; translation; DISCOVERY; insights; platform; chip

摘要

Despite unprecedented technological progress, most drug candidates continue to fail in clinical trials, reflecting a persistent gap between preclinical models and human biology. New approach methodologies (NAMs), by spanning human-derived cellular systems, microphysiological platforms, and artificial intelligence, offer a paradigm shift in human-centric drug development and biomedical research. Recent regulatory reforms, such as the US Food and Drug Administration (FDA) Modernization Act 3.0, have begun to position NAMs as a complement to or replacement for animal testing. This Review synthesizes emerging biological and computational NAMs and examines how their integration is reshaping drug development. We also discuss regulatory and ethical frameworks enabling this transition and outline a roadmap for embedding human-based science in a predictive, efficient, and ethically grounded infrastructure of human-centered drug development.