Skip to content
DraconiticResearch
Search Sources API
181,686 studies31 sourcesUpdated 26 min ago
Peer-reviewedCC BY-NC-NDSignal transduction and targeted therapy

Cancer-associated fibroblasts: origins, functional heterogeneity and therapeutic potential.

  • Liting Zhou1,2,3,4
  • Mengyue Tang1,3,4,5
  • Keke Wang4
  • Nan Wang6
  • Jiachen Zhang1,4,5
  • Kangdong Liu1,3,4,7,8,9
  • Xiang Li10,11,12,13,14,15
  • Zigang Dong16,17,18,19,20,21
21 affiliations
  1. 1State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
  2. 2Department of Medical Genetics & Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  3. 3Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Bio-medical Sciences, Cancer Prevention and Treatment Lab, Zhengzhou University, Zhengzhou, China.
  4. 4China‒US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.
  5. 5Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  6. 6Department of Radiation Oncology, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.
  7. 7Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  8. 8The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, China.
  9. 9State Key Laboratory of Esophageal Cancer Prevention and Treatment, Cancer Prevention and Treatment Lab, Zhengzhou University, Zhengzhou, China.
  10. 10State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. [email protected].
  11. 11Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Bio-medical Sciences, Cancer Prevention and Treatment Lab, Zhengzhou University, Zhengzhou, China. [email protected].
  12. 12China‒US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China. [email protected].
  13. 13Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. [email protected].
  14. 14The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, China. [email protected].
  15. 15State Key Laboratory of Esophageal Cancer Prevention and Treatment, Cancer Prevention and Treatment Lab, Zhengzhou University, Zhengzhou, China. [email protected].
  16. 16State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. [email protected].
  17. 17Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Bio-medical Sciences, Cancer Prevention and Treatment Lab, Zhengzhou University, Zhengzhou, China. [email protected].
  18. 18China‒US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China. [email protected].
  19. 19Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. [email protected].
  20. 20The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, China. [email protected].
  21. 21State Key Laboratory of Esophageal Cancer Prevention and Treatment, Cancer Prevention and Treatment Lab, Zhengzhou University, Zhengzhou, China. [email protected].
Read full textPDFDOICite

Abstract

Cancer-associated fibroblasts (CAFs) are integral components of the tumor microenvironment (TME) and are increasingly recognized as critical regulators of nearly every hallmark of cancer. Once viewed as a uniform, protumorigenic cell type, it is now clear that CAFs comprise a spectrum of dynamic and plastic functional states with both tumor-promoting and tumor-restraining capacities. This functional duality, conceptualized within the framework of cancer as a "wound that fails to heal", is dictated by their diverse cellular origins, the specific activation pathways engaged (such as TGF-β and PDGF), and the evolving cues from the TME. In this Review, we dissect the multifaceted roles of CAFs, from their promotion of cancer cell proliferation, invasion and angiogenesis through secreted factors and extensive extracellular matrix (ECM) remodeling, to their profound influence on the immune landscape. We detail how distinct CAF subsets, such as myofibroblastic (myCAFs) and inflammatory (iCAFs) CAFs, orchestrate an immunosuppressive niche and contribute to therapeutic resistance. We also explore the compelling evidence for tumor-suppressive CAF functions, which have catalyzed a paradigm shift in therapeutic strategies-moving away from indiscriminate CAF ablation towards nuanced approaches aimed at reprogramming their state. These strategies include modulating key signaling pathways, normalizing the CAF-remodeled ECM, and exploiting unique metabolic vulnerabilities. Finally, we discuss how advances in single-cell and spatial transcriptomics are resolving this complexity, paving the way for the development of precision therapies that can selectively neutralize pro-tumorigenic CAF activities while harnessing their beneficial functions to improve patient outcomes.

Related

  1. Type 2 Deiodinase in Cancer-Associated Fibroblasts: A Potential Therapeutic Target in Many Types of Cancer
    M. G. Carroll, N. Mukhtar, J. Calhoun +29
    medRxivPreprintAll rights reservedFull textOncologymedRxiv
  2. Cancer-associated fibroblasts in triple-negative breast cancer: heterogeneity, tumor-stroma crosstalk, and therapeutic resistance
    Shijie Wei, Xiaoqing Xie, Yufeng Cao +1
    Frontiers in OncologyPeer-reviewedCC BY 4.0Full textOncologyCrossrefEurope PMCPMC
  3. Recent advances in cancer-associated fibroblasts in colorectal cancer: functional subtypes, spatiotemporal dynamics and therapeutic targets.
    Yuang Ding, Shaohui Zhang, Yanfeng Guo +6
    Neoplasia (New York, N.Y.)Peer-reviewedCC BY-NC-NDFull textOncologyEurope PMC
  4. Cancer-Associated Fibroblasts in Perineural Invasion: Biological Roles and Therapeutic Strategies
    Xinxing Cui, Yun He, Liu Yang +2
    CellsPeer-reviewedCC BY 4.0Full textPsychiatry & mental healthCrossrefEurope PMC
  5. Cancer-associated fibroblasts: multifaceted regulators of the tumor microenvironment and emerging therapeutic targets
    Jinsong Yu, Han Yang, Xiaofang Zhu
    Frontiers in ImmunologyPeer-reviewedCC BY 4.0OncologyCrossref

Cite

BibTeXRIS
BibTeX
@article{zhou2026cancerassociated,
  title = {{Cancer-associated fibroblasts: origins, functional heterogeneity and therapeutic potential.}},
  author = {Liting Zhou and Mengyue Tang and Keke Wang and Nan Wang and Jiachen Zhang and Kangdong Liu and Xiang Li and Zigang Dong},
  journal = {Signal transduction and targeted therapy},
  year = {2026},
  month = oct,
  doi = {10.1038/s41392-026-02743-z},
  url = {https://europepmc.org/article/MED/42957652},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Cancer-associated fibroblasts: origins, functional heterogeneity and therapeutic potential.
AU  - Liting Zhou
AU  - Mengyue Tang
AU  - Keke Wang
AU  - Nan Wang
AU  - Jiachen Zhang
AU  - Kangdong Liu
AU  - Xiang Li
AU  - Zigang Dong
PY  - 2026
DA  - 2026/10/30
JO  - Signal transduction and targeted therapy
DO  - 10.1038/s41392-026-02743-z
UR  - https://europepmc.org/article/MED/42957652
AB  - Cancer-associated fibroblasts (CAFs) are integral components of the tumor microenvironment (TME) and are increasingly recognized as critical regulators of nearly every hallmark of cancer. Once viewed as a uniform, protumorigenic cell type, it is now clear that CAFs comprise a spectrum of dynamic and plastic functional states with both tumor-promoting and tumor-restraining capacities. This functional duality, conceptualized within the framework of cancer as a "wound that fails to heal", is dictated by their diverse cellular origins, the specific activation pathways engaged (such as TGF-β and PDGF), and the evolving cues from the TME. In this Review, we dissect the multifaceted roles of CAFs, from their promotion of cancer cell proliferation, invasion and angiogenesis through secreted factors and extensive extracellular matrix (ECM) remodeling, to their profound influence on the immune landscape. We detail how distinct CAF subsets, such as myofibroblastic (myCAFs) and inflammatory (iCAFs) CAFs, orchestrate an immunosuppressive niche and contribute to therapeutic resistance. We also explore the compelling evidence for tumor-suppressive CAF functions, which have catalyzed a paradigm shift in therapeutic strategies-moving away from indiscriminate CAF ablation towards nuanced approaches aimed at reprogramming their state. These strategies include modulating key signaling pathways, normalizing the CAF-remodeled ECM, and exploiting unique metabolic vulnerabilities. Finally, we discuss how advances in single-cell and spatial transcriptomics are resolving this complexity, paving the way for the development of precision therapies that can selectively neutralize pro-tumorigenic CAF activities while harnessing their beneficial functions to improve patient outcomes.
SN  - 2095-9907
SN  - 2059-3635
ER  -