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Cited by 49Liver physiology and pathologyHepatocellular Carcinoma Treatment and PrognosisCholangiocarcinoma and Gallbladder Cancer Studies

Fibroblasts in liver cancer: functions and therapeutic translation

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Affo, Silvia, Filliol, Aveline, Gores, Gregory J, Schwabe, Robert F·2023·The Lancet Gastroenterology & Hepatology
DOI 10.1016/s2468-1253(23)00111-5PMC PMC11809766
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Abstract

Accumulation of fibroblasts in the premalignant or malignant liver is a characteristic feature of liver cancer, but has not been therapeutically leveraged despite evidence for pathophysiologically relevant roles in tumour growth. Hepatocellular carcinoma is a largely non-desmoplastic tumour, in which fibroblasts accumulate predominantly in the pre-neoplastic fibrotic liver and regulate the risk for hepatocellular carcinoma development through a balance of tumour-suppressive and tumour-promoting mediators. By contrast, cholangiocarcinoma is desmoplastic, with cancer-associated fibroblasts contributing to tumour growth. Accordingly, restoring the balance from tumour-promoting to tumour-suppressive fibroblasts and mediators might represent a strategy for hepatocellular carcinoma prevention, whereas in cholangiocarcinoma, fibroblasts and their mediators could be leveraged for tumour treatment. Importantly, fibroblast mediators regulating hepatocellular carcinoma development might exert opposite effects on cholangiocarcinoma growth. This Review translates the improved understanding of tumour-specific, location-specific, and stage-specific roles of fibroblasts and their mediators in liver cancer into novel and rational therapeutic concepts.

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Authors
Affo, S., Filliol, A., Gores, G. J., & Schwabe, R. F.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Mayo Clinic (US)
  • Columbia University Irving Medical Center (US)
Corresponding author
Schwabe, Robert F
ORCID
Venue
The Lancet Gastroenterology & Hepatology
Publisher
Elsevier BV
Published
2023-08
Volume
8
Issue
8
Pages
748-759
ISSN
  • 2468-1156 (ISSN-L)
  • 2468-1253
DOI
10.1016/s2468-1253(23)00111-5
PMC
PMC11809766
OpenAlex
W4382045916
Cited by
49
References
86
Citations by year
2026: 14 · 2025: 24 · 2024: 9 · 2023: 2
FWCI
2.12
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet. Gastroenterology & hepatology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
Funders
  • European Union
  • NIH
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
Keywords
liver cancer, cancer-associated fibroblasts, hepatocellular carcinoma, cholangiocarcinoma, liver fibrosis, desmoplasia, tumor microenvironment, tumor suppression, tumor promotion, hepatocellular carcinoma prevention, therapeutic translation
MeSH terms
Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Fibroblasts, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Cholangiocarcinoma

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