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Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies

Oncogene volume 32, pages 4861–4870 (2013)Cite this article

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Abstract

Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with very poor prognosis. Genome-wide, high-throughput technologies have made major advances in understanding the molecular basis of this disease, although important mechanisms are still unclear. Recent data have revealed specific genetic mutations (for example, KRAS, IDH1 and IDH2), epigenetic silencing, aberrant signaling pathway activation (for example, interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), tyrosine kinase receptor-related pathways) and molecular subclasses with unique alterations (for example, proliferation and inflammation subclasses). In addition, some ICCs share common genomic traits with hepatocellular carcinoma. All this information provides the basis to explore novel targeted therapies. Currently, surgery at early stage is the only effective therapy. At more advanced stages, chemotherapy regimens are emerging (that is, cisplatin plus gemcitabine), along with molecular targeted agents tested in several ongoing clinical trials. Nonetheless, a first-line conclusive treatment remains an unmet need. Similarly, there are no studies assessing tumor response related with genetic alterations. This review explores the recent advancements in the knowledge of the molecular alterations underlying ICC and the future prospects in terms of therapeutic strategies leading towards a more personalized treatment of this neoplasm.

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Acknowledgements

Josep M Llovet is supported by grants from the US National Institutes of Diabetes and Digestive and Kidney Diseases (1R01DK076986), the European Commission’s Framework Programme 7 (HEPTROMIC; 259744), the Asociación Española Contra el Cáncer, the Spanish National Health Institute (SAF-2010-16055) and the Samuel Waxman Cancer Research Foundation.

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  1. HCC Translational Research Laboratory, Liver Unit, Barcelona-Clinic Liver Cancer Group, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Catalonia, Spain

    D Sia, V Tovar, A Moeini & J M Llovet

  2. Gastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute, Milan, Italy

    D Sia

  3. Mount Sinai Liver Cancer Program [Divisions of Liver Diseases], Department of Medicine, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA

    J M Llovet

  4. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain

    J M Llovet

  5. University of Barcelona, Barcelona, Catalonia, Spain

    J M Llovet

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Sia, D., Tovar, V., Moeini, A. et al. Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene 32, 4861–4870 (2013). https://doi.org/10.1038/onc.2012.617

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