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Annual Review of Pharmacology and Toxicology

Volume 65, 2025

Next-Gen Therapeutics: Pioneering Drug Discovery with iPSCs, Genomics, AI, and Clinical Trials in a Dish

  • Zehra Yildirim1, Kyle Swanson2,3, Xuekun Wu1, James Zou2 and Joseph Wu1
  • 1Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA; email: [email protected] 2Department of Computer Science, Stanford University, Stanford, California, USA 3Greenstone Biosciences, Palo Alto, California, USA
  • Vol. 65:71-90 (Volume publication date January 2025)
  • First published as a Review in Advance on September 16, 2024
  • Copyright © 2025 by Greenstone Biosciences, Inc.
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

In the high-stakes arena of drug discovery, the journey from bench to bedside is hindered by a daunting 92% failure rate, primarily due to unpredicted toxicities and inadequate therapeutic efficacy in clinical trials. The FDA Modernization Act 2.0 heralds a transformative approach, advocating for the integration of alternative methods to conventional animal testing, including cell-based assays that employ human induced pluripotent stem cell (iPSC)-derived organoids, and organ-on-a-chip technologies, in conjunction with sophisticated artificial intelligence (AI) methodologies. Our review explores the innovative capacity of iPSC-derived clinical trial in a dish models designed for cardiovascular disease research. We also highlight how integrating iPSC technology with AI can accelerate the identification of viable therapeutic candidates, streamline drug screening, and pave the way toward more personalized medicine. Through this, we provide a comprehensive overview of the current landscape and future implications of iPSC and AI applications being navigated by the research community and pharmaceutical industry.

Keyword(s): cardiotoxicity, clinical trials in a dish, drug discovery, iPSC
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2025-01-23
2025-06-14
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/content/journals/10.1146/annurev-pharmtox-022724-095035
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Next-Gen Therapeutics: Pioneering Drug Discovery with iPSCs, Genomics, AI, and Clinical Trials in a Dish
Annual Review of Pharmacology and Toxicology 65, 71 (2025); https://doi.org/10.1146/annurev-pharmtox-022724-095035
/content/journals/10.1146/annurev-pharmtox-022724-095035
/content/journals/10.1146/annurev-pharmtox-022724-095035
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