Abstract
Fibrosis is a pathophysiological mechanism involved in chronic and progressive diseases that results in excessive tissue scarring. Diseases associated with fibrosis include metabolic dysfunction-associated steatohepatitis (MASH), inflammatory bowel diseases (IBDs), chronic kidney disease (CKD), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), which are collectively responsible for substantial morbidity and mortality. Although a few drugs with direct antifibrotic activity are approved for pulmonary fibrosis and considerable progress has been made in the understanding of mechanisms of fibrosis, translation of this knowledge into effective therapies continues to be limited and challenging. With the aim of assisting developers of novel antifibrotic drugs, this Review integrates viewpoints of biologists and physician-scientists on core pathways involved in fibrosis across organs, as well as on specific characteristics and approaches to assess therapeutic interventions for fibrotic diseases of the lung, gut, kidney, skin and liver. This discussion is used as a basis to propose strategies to improve the translation of potential antifibrotic therapies.
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Change history
31 March 2025
A Correction to this paper has been published: https://doi.org/10.1038/s41573-025-01190-9
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Acknowledgements
The authors thank the Helmsley Charitable Trust for supporting the construction of a pathway to test antifibrotic therapies in IBD. The research of L.E.N. is funded in part by grants from NIH P50AA024333, R01AA027456, U01AA026398 and R01AA030699. B.H.’s research is supported by grants from the Canadian Institutes of Health Research CIHR (#375597, #190081) and joint support from the Canada Foundation for Innovation (CFI) and the Ontario Research Fund (ORF) (#36050, #38861, #36349). T.M.M. is supported by an NIHR Clinician Scientist Fellowship (NIHR Ref: CS-2013-13-017) British Lung Foundation Chair in Respiratory Research (C17-3).
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F.R. is on the advisory board of or consultant to Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, AstraZeneca, Bausch & Lomb, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Eugit, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Janssen, Koutif, Mestag, Metacrine, Mirum, Mopac, Morphic, Myka Labs, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, Trix Bio, UCB, Ysios and 89Bio. J.H.W.D. has consultancy relationships with and/or is part of the speaker or advisory board of AbbVie, Active Biotech, Anamar, ARXX, AstraZeneca, Bayer Pharma, Boehringer-Ingelheim, Calliditas Therapeutics, Celgene, Galapagos, Genentech, GSK, Inventiva, Janssen, Novartis, Pfizer, Roche and UCB. J.H.W.D. has received research funding from Anamar, Argenx, ARXX, BMS, Bayer Pharma, Boehringer-Ingelheim, Cantargia, Celgene, CSL Behring, Galapagos, GSK, Inventiva, Kiniksa, Lassen, Sanofi-Aventis, RedX and UCB. J.H.W.D. is CEO of 4D Science and Scientific Lead of FibroCure. R.K. is founder and shareholder of Sequantrix GmbH and has grants from Travere Therapeutics, Galapagos, Chugai, AskBio and Novo Nordisk and is a consultant for Bayer, Roche, Chugai, Pfizer, Novo Nordisk, Hybridize Therapeutics and Gruenenthal. T.M.M., via his institution, has received industry-academic funding from AstraZeneca and GlaxoSmithKline R&D; and consultancy or speaker fees from AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, CSL Behring, Fibrogen, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Merck, Pliant, Pfizer, Qureight, Roche, Sanofi-Aventis, Structure Therapeutics, Trevi and Veracyte. M.P. is an employee of Medicxi Ventures. L.E.N. and B.H. declare no competing interests.
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Pliant Therapeutics provides update on BEACON-IPF, a phase 2b/3 trial in patients with idiopathic pulmonary fibrosis: https://ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-provides-update-beacon-ipf-phase-2b3-trial-0
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Rieder, F., Nagy, L.E., Maher, T.M. et al. Fibrosis: cross-organ biology and pathways to development of innovative drugs. Nat Rev Drug Discov 24, 543–569 (2025). https://doi.org/10.1038/s41573-025-01158-9
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DOI: https://doi.org/10.1038/s41573-025-01158-9
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