Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies

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. Access through your institution Buy or

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CHOLANGIOCARCINOMA 2020: THE NEXT HORIZON IN MECHANISMS AND MANAGEMENT Article Open access 30 June 2020 MOLECULAR PROFILE AND ITS CLINICAL IMPACT OF IDH1 MUTATED VERSUS IDH1 WILD TYPE

INTRAHEPATIC CHOLANGIOCARCINOMA Article Open access 05 November 2022 PRECISION ONCOLOGY FOR INTRAHEPATIC CHOLANGIOCARCINOMA IN CLINICAL PRACTICE Article Open access 19 August 2022 REFERENCES

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Oncol_ 2012; 23: 2341–2346. CAS  PubMed  Google Scholar  Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * Gastrointestinal

Surgery and Liver Transplantation Unit, National Cancer Institute, Milan, Italy D Sia * 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 * Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain J M Llovet * University of Barcelona,

Barcelona, Catalonia, Spain J M Llovet Authors * D Sia View author publications You can also search for this author inPubMed Google Scholar * V Tovar View author publications You can also

search for this author inPubMed Google Scholar * A Moeini View author publications You can also search for this author inPubMed Google Scholar * J M Llovet View author publications You can

also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to J M Llovet. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 28 September 2012 * Revised: 08 November 2012 * Accepted: 15 November

2012 * Published: 14 January 2013 * Issue Date: 10 October 2013 * DOI: https://doi.org/10.1038/onc.2012.617 SHARE THIS ARTICLE Anyone you share the following link with will be able to read

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KEYWORDS * cholangiocarcinoma * molecular pathogenesis * targeted therapies