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Peer-reviewedCC BY-NC-NDMolecular cancer

The bright side of the stroma: the tumor-suppressive roles of cancer-associated fibroblasts.

  • Tommy Chastel1
  • Lena-Marie Schmitt1,2
  • Constanze Leonie Augenstein1
  • Richard Tomasini3
  • Andrei Turtoi4,5
5 affiliations
  1. 1Tumor Microenvironment and Resistance to Treatment Laboratory, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, University of Montpellier, Montpellier, France.
  2. 2Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
  3. 3Cancer Research Centre of Marseille, INSERM U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France.
  4. 4Tumor Microenvironment and Resistance to Treatment Laboratory, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, University of Montpellier, Montpellier, France. [email protected].
  5. 5Gunma University Initiative for Advanced Research (GIAR), Gunma University, 3-39-22 Showamachi, Maebashi, Gunma, 371-8511, Japan. [email protected].
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Abstract

In the past decades, cancer-associated fibroblasts (CAFs) have emerged as central regulators of the tumor microenvironment (TME). CAFs have been implicated in extracellular matrix (ECM) remodeling, cytokine secretion and the establishment of the desmoplastic niche that supports tumor progression. Consequently, for long time, therapeutic strategies have focused on CAF depletion. However, accumulating evidence have demonstrated that indiscriminate targeting of CAFs can accelerate tumor progression, revealing their functional heterogeneity and a previously underappreciated tumor-restraining role. In this review, we examine the evolving paradigm of CAF biology, highlighting emerging tumor-suppressive CAF subtypes and their underlying mechanisms. We discuss how these findings challenge conventional therapeutic strategies and propose, based on this improved CAF stratification, a conceptual shift toward CAF exploitation rather than elimination. Ultimately, harnessing CAF anti-tumoral properties may open new avenues for more effective and context-specific cancer therapies.

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Cite

BibTeXRIS
BibTeX
@article{chastel2026bright,
  title = {{The bright side of the stroma: the tumor-suppressive roles of cancer-associated fibroblasts.}},
  author = {Tommy Chastel and Lena-Marie Schmitt and Constanze Leonie Augenstein and Richard Tomasini and Andrei Turtoi},
  journal = {Molecular cancer},
  year = {2026},
  month = aug,
  doi = {10.1186/s12943-026-02769-5},
  url = {https://europepmc.org/article/MED/43009995},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - The bright side of the stroma: the tumor-suppressive roles of cancer-associated fibroblasts.
AU  - Tommy Chastel
AU  - Lena-Marie Schmitt
AU  - Constanze Leonie Augenstein
AU  - Richard Tomasini
AU  - Andrei Turtoi
PY  - 2026
DA  - 2026/08/13
JO  - Molecular cancer
DO  - 10.1186/s12943-026-02769-5
UR  - https://europepmc.org/article/MED/43009995
AB  - In the past decades, cancer-associated fibroblasts (CAFs) have emerged as central regulators of the tumor microenvironment (TME). CAFs have been implicated in extracellular matrix (ECM) remodeling, cytokine secretion and the establishment of the desmoplastic niche that supports tumor progression. Consequently, for long time, therapeutic strategies have focused on CAF depletion. However, accumulating evidence have demonstrated that indiscriminate targeting of CAFs can accelerate tumor progression, revealing their functional heterogeneity and a previously underappreciated tumor-restraining role. In this review, we examine the evolving paradigm of CAF biology, highlighting emerging tumor-suppressive CAF subtypes and their underlying mechanisms. We discuss how these findings challenge conventional therapeutic strategies and propose, based on this improved CAF stratification, a conceptual shift toward CAF exploitation rather than elimination. Ultimately, harnessing CAF anti-tumoral properties may open new avenues for more effective and context-specific cancer therapies.
SN  - 1476-4598
ER  -