Cited by 1,265Cancer Cells and MetastasisTGF-β signaling in diseasesPancreatic and Hepatic Oncology Research

Diversity and biology of cancer-associated fibroblasts

Open access
Biffi, Giulia, Tuveson, David A.·2021·Physiological Reviews

Abstract

Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite the presence of non-neoplastic stromal components that substantially contribute to the progression of the tumor. Indeed, cancer cell survival, growth, migration, and even dormancy are influenced by the surrounding tumor microenvironment (TME). Within the TME, cancer-associated fibroblasts (CAFs) have been shown to play several roles in the development of a tumor. They secrete growth factors, inflammatory ligands, and extracellular matrix proteins that promote cancer cell proliferation, therapy resistance, and immune exclusion. However, recent work indicates that CAFs may also restrain tumor progression in some circumstances. In this review, we summarize the body of work on CAFs, with a particular focus on the most recent discoveries about fibroblast heterogeneity, plasticity, and functions. We also highlight the commonalities of fibroblasts present across different cancer types, and in normal and inflammatory states. Finally, we present the latest advances regarding therapeutic strategies targeting CAFs that are undergoing preclinical and clinical evaluation.

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Registry

Crossref · 10.1152/physrev.00048.2019

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345 of 345 references verified0 citation errors · 0 not checkable

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Authors
Biffi, G., & Tuveson, D. A.
Affiliations
University of Cambridge (GB)
Corresponding author
  • Biffi, Giulia
  • Tuveson, David A.
Venue
Physiological Reviews
Published
2021-01-01
Volume
101
Issue
1
Pages
147-176
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
OpenAlex
W3031767666
Cited by
1,265
References
345
Citations by year
2026: 227 · 2025: 241 · 2024: 274 · 2023: 258 · 2022: 188 · 2021: 71 · 2020: 5
FWCI
14.56
Type
journal article
Language
en
Open access
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
Funders
  • HHS | National Institutes of Health (5P30CA045508)
  • Lustgarten Foundation
  • CSHL and Northwell Health Affiliation
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
cancer-associated fibroblasts, tumor microenvironment, fibroblast heterogeneity, fibroblast plasticity, extracellular matrix, treatment resistance, immune exclusion, tumor progression, CAF-targeted therapy
MeSH terms
Cancer-Associated Fibroblasts, Animals, Antineoplastic Agents, Humans, Neoplasms, Cell Proliferation, Tumor Microenvironment

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