Cancer-Associated Fibroblasts: Mechanisms, Plasticity, and Therapeutic Targeting in Cancer Progression

Cancer-associated fibroblasts (CAFs) are among the most abundant and dynamic stromal cell populations within the tumor microenvironment. Beyond providing structural support, CAFs actively regulate extracellular matrix remodeling, tumor cell plasticity, angiogenesis, immune suppression, metabolic adaptation, and therapy resistance. Recent advances in single-cell sequencing, spatial transcriptomics, and multi-omics technologies have revealed remarkable heterogeneity and functional plasticity among CAF populations across different cancer types. These discoveries have challenged the traditional view of CAFs as a uniformly tumor-promoting population and highlighted the context-dependent roles of distinct CAF subsets in tumor progression, metastasis, and therapeutic response. Meanwhile, emerging strategies targeting CAFs, stromal signaling pathways, extracellular matrix remodeling, and CAF-mediated immune regulation have demonstrated promising potential in preclinical and early clinical studies. Nevertheless, many fundamental questions regarding CAF biology, intercellular communication, and clinical translation remain unresolved.This Research Topic aims to provide a comprehensive platform for presenting recent advances in the biological functions, molecular mechanisms, and translational implications of cancer-associated fibroblasts in solid tumors. We particularly welcome studies addressing the origin, heterogeneity, lineage plasticity, and stress adaptation of CAFs, as well as their interactions with tumor cells, immune cells, endothelial cells, and the extracellular matrix. We also encourage research investigating how CAFs regulate tumor metabolism, mechanotransduction, therapy resistance, and metastatic progression. Particular interest will be given to studies employing emerging technologies, including single-cell multi-omics, spatial transcriptomics, organoid systems, organ-on-chip models, and artificial intelligence-assisted analyses. In addition, this Research Topic seeks to highlight innovative therapeutic strategies targeting CAFs or stromal remodeling, including small molecules, monoclonal antibodies, peptides, nanomedicines, and rational combination therapies. By integrating mechanistic discoveries with translational and clinical research, this collection aims to identify key stromal vulnerabilities, uncover new therapeutic opportunities, and facilitate the development of precision stromal-targeted cancer therapies.We welcome Original Research, Reviews, Mini Reviews, and Perspectives focusing on:1. CAF heterogeneity, lineage tracing, cellular plasticity, and stress adaptation. 2. Molecular mechanisms governing CAF activation and stromal remodeling. 3. Crosstalk between CAFs and tumor cells, immune cells, endothelial cells, and the extracellular matrix. 4. CAF-mediated regulation of tumor metabolism, extracellular matrix remodeling, mechanotransduction, and metastatic progression. 5. Single-cell multi-omics, spatial transcriptomics, and AI-assisted approaches for CAF research.6. Organoid and organ-on-chip models for studying CAF biology and tumor–stroma interactions. 7. CAF-targeted therapeutic strategies, including antibodies, peptides, nanomedicines, and combination therapies.8. Biomarkers and clinical translation of CAF-targeted precision oncology. Topic editors: Chengsheng Wu, Haifeng Zhang, Xu Cao Source: https://www.frontiersin.org/research-topics/84586/cancer-associated-fibroblasts-mechanisms-plasticity-and-therapeutic-targeting-in-cancer-progression