The evolving role of investigative toxicology in the pharmaceutical industry

作者：François Pognan, Mario Beilmann, Harrie C. M. Boonen, Andreas Czich, Gordon J. Dear, Philip Hewitt, Tomas Mow, Teija Oinonen, Adrian Roth, Thomas Steger‐Hartmann, Jean‐Pierre Valentin, Freddy Van Goethem, Richard Weaver, Peter Newham · 发表于：Nature Reviews Drug Discovery · 年份：2023 · DOI：10.1038/s41573-022-00633-x · 被引用次数：252 · 研究领域：3D Printing in Biomedical Research、Computational Drug Discovery Methods、Cell Image Analysis Techniques

For decades, preclinical toxicology was essentially a descriptive discipline in which treatment-related effects were carefully reported and used as a basis to calculate safety margins for drug candidates. In recent years, however, technological advances have increasingly enabled researchers to gain insights into toxicity mechanisms, supporting greater understanding of species relevance and translatability to humans, prediction of safety events, mitigation of side effects and development of safety biomarkers. Consequently, investigative (or mechanistic) toxicology has been gaining momentum and is now a key capability in the pharmaceutical industry. Here, we provide an overview of the current status of the field using case studies and discuss the potential impact of ongoing technological developments, based on a survey of investigative toxicologists from 14 European-based medium-sized to large pharmaceutical companies. Investigative toxicology tools and strategies are used in pharmaceutical companies to reduce safety-related attrition in drug development. This Perspective article summarizes the key goals of investigative toxicology, highlights current approaches and discusses selected emerging technologies that have the potential to improve the current safety-testing paradigm.