Drug repurposing in fibrosis: From molecular networks to antifibrotic therapeutics—A narrative review

Abstract

Fibrosis is a common pathological endpoint of chronic diseases affecting multiple organs and remains a major cause of morbidity and mortality worldwide. Despite advances in understanding fibrogenesis, current antifibrotic therapies primarily slow rather than reverse disease progression, underscoring the need for more effective treatments. Drug repurposing offers a promising strategy by leveraging the established safety and pharmacokinetic profiles of approved drugs while reducing development time and cost. This review provides a mechanism‐based synthesis of repurposed agents targeting the interconnected pathways driving fibrosis, including transforming growth factor‐ β signalling, chronic inflammation, oxidative stress and emerging regulatory networks such as mechanotransduction and cellular senescence. Evidence from mechanistic studies, preclinical models, randomized trials and meta‐analyses is critically appraised, highlighting promising candidates and translational challenges arising from the distinct cellular mechanisms and variable reversibility of fibrosis across organs. By integrating molecular insights with clinical evidence, this review advocates a pathway‐guided, biomarker‐driven approach to drug repurposing as a rational strategy for accelerating development of personalized, multi‐target antifibrotic therapies.