Cited by 1,230Cancer Cells and MetastasisPancreatic and Hepatic Oncology ResearchTGF-β signaling in diseases

Clinical and therapeutic relevance of cancer-associated fibroblasts

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Chen, Yang, McAndrews, Kathleen M., Kalluri, Raghu·2021·Nature Reviews Clinical Oncology

Abstract

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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  1. [30]Tarin D & Croft CB Ultrastructural features of wound healing in mouse skin. J. Anat 105, 189– 190 (1969). 5803198

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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
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
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

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