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Cholangiocarcinoma

Nature Reviews Disease Primers volume 7, Article number: 65 (2021) Cite this article

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Abstract

Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations and therapeutic approaches. In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration of the anthelmintic drug praziquantel decreases the risk of CCA from liver flukes, but reinfection is common and future vaccination strategies may be more effective. Some patients with CCA are eligible for potentially curative surgical options, such as resection or liver transplantation. Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. CCA is a highly desmoplastic cancer and targeting the tumour immune microenvironment might be a promising therapeutic approach. CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes.

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Fig. 1: Anatomic subtypes of CCA.
Fig. 2: Pathophysiology of liver-fluke infection and CCA.
Fig. 3: CCA cells gradually adopt invasive phenotypes to metastasize.
Fig. 4: Histological features of the desmoplastic microenvironment in human iCCA.
Fig. 5: Screening for liver fluke infection and associated hepatobiliary disease including CCA.

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Acknowledgements

G.J.G. is supported by the SPORE grant CA210964. P.J.B. and A.L. receive grant support (R01CA164719) from the National Institute of Health. S.A.K. is grateful for support from the UK National Institute for Health Research (NIHR) Biomedical Facilities at Imperial College London. B.T.T. receives support from The National Medical Research Council (grant MOH-000248). S.I.I. receives support from the National Cancer Institute (1K08CA236874) and the Mayo Foundation. A.L. receives support from National Health and Medical Research Council Senior Principal Research Fellowship 1117504. S.W. receives support from National Science and Technology Development Agency (NSTDA), Thailand, and the e-ASIA JRP.

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Authors and Affiliations

  1. Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA

    Paul J. Brindley

  2. Cholangiocarcinoma Foundation, Salt Lake City, UT, USA

    Melinda Bachini

  3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Sumera I. Ilyas & Gregory J. Gores

  4. Liver Unit, Division of Digestive Diseases, Imperial College London, London, UK

    Shahid A. Khan

  5. Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia

    Alex Loukas

  6. Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Alphonse E. Sirica

  7. Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre, Singapore, Singapore

    Bin Tean Teh

  8. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

    Sopit Wongkham

Authors
  1. Paul J. Brindley
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  2. Melinda Bachini
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  6. Alphonse E. Sirica
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  8. Sopit Wongkham
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  9. Gregory J. Gores
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Contributions

Introduction (G.J.G.); Epidemiology (P.J.B. and S.A.K.); Mechanisms/pathophysiology (B.T.T., A.L., S.W. and A.E.S.); Diagnosis, screening and prevention (S.I.I., P.J.B. and G.J.G.); Management (S.I.I.); Quality of life (M.B.); Outlook (G.J.G.); Overview of Primer (G.J.G.).

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Correspondence to Gregory J. Gores.

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Nature Reviews Disease Primers thanks B. Koerkamp; D.-Y. Oh, who co-reviewed with J. Yoon; R. T. Shroff, who co-reviewed with M. Savani; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Brindley, P.J., Bachini, M., Ilyas, S.I. et al. Cholangiocarcinoma. Nat Rev Dis Primers 7, 65 (2021). https://doi.org/10.1038/s41572-021-00300-2

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