Shalini T, Sudhandiran G. Provoking myofibroblast death: Strategies to resolve fibrosis and remodel tumor microenvironment. World J Clin Oncol 2025; 16(12): 111086 [DOI: 10.5306/wjco.v16.i12.111086]
Corresponding Author of This Article
Ganapasam Sudhandiran, PhD, Professor, Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nādu, India. sudhandiran@yahoo.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Dec 24, 2025; 16(12): 111086 Published online Dec 24, 2025. doi: 10.5306/wjco.v16.i12.111086
Provoking myofibroblast death: Strategies to resolve fibrosis and remodel tumor microenvironment
Thangavelu Shalini, Ganapasam Sudhandiran
Thangavelu Shalini, Department of Biochemistry, University of Madras, Chennai 600025, Tamil Nādu, India
Ganapasam Sudhandiran, Cell Biology Laboratory, Department of Biochemistry, University of Madras, Chennai 600025, Tamil Nādu, India
Author contributions: Shalini T and Sudhandiran G contributed equally to the conception, literature collection, manuscript drafting, and critical revisions; and all authors approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ganapasam Sudhandiran, PhD, Professor, Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nādu, India. sudhandiran@yahoo.com
Received: June 23, 2025 Revised: July 28, 2025 Accepted: November 13, 2025 Published online: December 24, 2025 Processing time: 183 Days and 21.2 Hours
Abstract
Fibrosis is marked by the excessive accumulation of extracellular matrix (ECM) components, leading to tissue scarring and progressive loss of organ function. Myofibroblasts, which emerge during tissue repair, are specialized contractile cells exhibiting features of both fibroblasts and smooth muscle cells. Their expression of α-smooth muscle actin facilitates contractile activity, while their persistent activation and overproduction of ECM components contribute significantly to pathological wound contraction and fibrotic progression. Beyond ECM production, myofibroblasts play a significant role in the tumor microenvironment (TME) of various solid tumors. The TME is a complex network of immune cells, blood vessels, ECM components, and stromal cells like fibroblasts and myofibroblasts that surrounds and interacts with cancer cells, thereby influencing tumor growth, progression, and therapy responsiveness. Through these interactions, myofibroblasts modulate inflammation, angiogenesis, and tissue remodeling. Maintaining myofibroblast homeostasis is therefore crucial, as its disruption can drive the onset of chronic fibrotic conditions and malignancies. This review explores preclinical and clinical developments in targeting myofibroblasts in fibrotic and TME across various disease models, including hypertrophic scar, idiopathic pulmonary fibrosis, oral submucous fibrosis, cardiac fibrosis, and the desmoplastic stroma of pancreatic and breast cancers.
Core Tip: Myofibroblasts are contractile cells that play a central role in both fibrosis and tumor progression due to their involvement in excessive extracellular matrix deposition and tissue stiffening. This article highlights emerging strategies to selectively inactivate or induce myofibroblast death, aiming to resolve fibrosis and remodel the tumor microenvironment. By exploring diverse disease models of fibrosis and cancer, this review underscores the therapeutic potential of targeting myofibroblasts to halt chronic tissue damage and improve cancer treatment outcomes.
