Clinical and therapeutic relevance of cancer-associated fibroblasts
Open accessAbstract
Cancer-associated fibroblasts (CAFs) found in primary and metastatic tumours are highly versatile, plastic and resilient cells that are actively involved in cancer progression through complex interactions with other cell types in the tumour microenvironment. As well as generating extracellular matrix components that contribute to the structure and function of the tumour stroma, CAFs undergo epigenetic changes to produce secreted factors, exosomes and metabolites that influence tumour angiogenesis, immunology and metabolism. Because of their putative pro-oncogenic functions, CAFs have long been considered an attractive therapeutic target; however, clinical trials of treatment strategies targeting CAFs have mostly ended in failure and, in some cases, accelerated cancer progression and resulted in inferior survival outcomes. Importantly, CAFs are heterogeneous cells and their characteristics and interactions with other cell types might change dynamically as cancers evolve. Studies involving single-cell RNA sequencing and novel mouse models have increased our understanding of CAF diversity, although the context-dependent roles of different CAF populations and their interchangeable plasticity remain largely unknown. Comprehensive characterization of the tumour-promoting and tumour-restraining activities of CAF subtypes, including how these complex bimodal functions evolve and are subjugated by neoplastic cells during cancer progression, might facilitate the development of novel diagnostic and therapeutic approaches. In this Review, the clinical relevance of CAFs is summarized with an emphasis on their value as prognosis factors and therapeutic targets.
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The enrichment of CMS4 tumors in CAFs is a shared outstanding characteristic.
“Whatever their intrinsic subtype correspondence, the enrichment of CMS4 tumors in CAFs is a shared outstanding characteristic.”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [55]
The immunosuppressive trait of CMS4 is reinforced by CAFs.
“it is likely that the immunosuppressive trait of CMS4 is reinforced by CAFs (55).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [55]
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- Authors
- Chen, Y., McAndrews, K. M., & Kalluri, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kalluri, Raghu
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2021-09-06
- Volume
- 18
- Issue
- 12
- Pages
- 792-804
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- PMC
- PMC8791784
- OpenAlex
- W3198094729
- Cited by
- 1,230
- References
- 168
- Citations by year
- 2026: 196 · 2025: 288 · 2024: 349 · 2023: 259 · 2022: 132 · 2021: 6
- FWCI
- 23.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA117969)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cancer-associated fibroblasts, tumor microenvironment, CAF heterogeneity, tumor stroma, extracellular matrix, exosomes, tumor angiogenesis, tumor immunology, cancer metabolism, CAF-targeted therapy, prognostic factors, CAF subpopulations, tumor progression
- MeSH terms
- Cancer-Associated Fibroblasts, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Epigenesis, Genetic, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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