Cited by 757Liver physiology and pathologyHepatocellular Carcinoma Treatment and PrognosisCholangiocarcinoma and Gallbladder Cancer Studies

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The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer

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Affo, Silvia, Yu, Le-Xing, Schwabe, Robert F.·2017·Annual Review of Pathology: Mechanisms of Disease

DOI 10.1146/annurev-pathol-052016-100322PMC PMC5720358

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Abstract

Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver. Cholangiocarcinoma (CCA), in contrast, is characterized by a strong desmoplasia that typically occurs in response to the tumor, suggesting a key role of cancer-associated fibroblasts (CAFs) and fibrosis in its tumor microenvironment (TME). Here, we discuss the functional contributions of myofibroblasts, CAFs, and fibrosis to the development of HCC and CCA in the hepatic PME and TME, focusing on myofibroblast- and extracellular matrix–associated growth factors, fibrosis-associated immunosuppressive pathways, as well as mechanosensitive signaling cascades that are activated by increased tissue stiffness. Better understanding of the role of myofibroblasts in HCC and CCA development and progression may provide the basis to target these cells for tumor prevention or therapy.

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Authors: Affo, S., Yu, L.-X., & Schwabe, R. F.
Affiliations: Department of Medicine, Columbia University, New York, NY 10032;
Columbia University (US)
ORCID: Yu, Le-Xing
Schwabe, Robert F.
Venue: Annual Review of Pathology: Mechanisms of Disease
Publisher: Annual Reviews
Published: 2017-01-24
Volume: 12
Issue: 1
Pages: 153-186
ISSN: 1553-4006 (ISSN-L)
1553-4014
DOI: 10.1146/annurev-pathol-052016-100322
PMC: PMC5720358
OpenAlex: W2411225414
Cited by: 757
References: 269
Citations by year: 2026: 62 · 2025: 97 · 2024: 96 · 2023: 107 · 2022: 104 · 2021: 94 · 2020: 101 · 2019: 48 · 2018: 36 · 2017: 12
FWCI: 3.99
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
Locations: Annual Review of Pathology Mechanisms of Disease (publishedVersion, cc-by)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA190844, R01CA200597)
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: cancer-associated fibroblasts, liver fibrosis, hepatocellular carcinoma, cholangiocarcinoma, tumor microenvironment, myofibroblasts, desmoplasia, extracellular matrix, growth factors, immunosuppression, mechanosensitive signaling, tissue stiffness, liver cirrhosis, liver cancer progression
MeSH terms: Cancer-Associated Fibroblasts, Animals, Humans, Liver Cirrhosis, Liver Neoplasms, Signal Transduction, Myofibroblasts, Tumor Microenvironment

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The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer

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