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Refining genetic and molecular classifications to facilitate breakthrough treatments in intrahepatic cholangiocarcinoma: are we there yet?
  1. Satoru Morita,
  2. Dan G Duda
  1. Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Dan G Duda, Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA; duda{at}

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Intrahepatic cholangiocarcinoma (ICC) is a type of biliary tract cancer and the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC). ICC incidence and mortality have been continuously increasing worldwide over the past decades.1 ICCs are rarely diagnosed early, and there is a high risk of distant recurrence even after complete surgical resection. Most ICC patients present with unresectable, advanced disease, for which the first-line treatment is systemic gemcitabine/cisplatin treatment. This combination chemotherapy is used for all biliary tract cancers and can delay tumour progression in many patients but is invariably followed by the development of treatment resistance. Genomic characterisation over the last decade had led to successful clinical development of molecularly targeted drugs in ICC, such as fibroblast growth factor receptor (FGFR) and isocitrate dehydrogenase (IDH) inhibitors for the treatment of FGFR-driven and IDH-driven ICCs, respectively.2 However, these drugs have also shown generally transient benefits in the advanced disease setting.3 4 Overall, the 5-year survival for advanced ICC is a dismal 5%. Clearly, improving ICC treatment will require additional progress and earlier intervention.

An attractive approach that may impact ICCs more broadly is the use of immunotherapy with immune checkpoint blockers (ICBs) to reactivate and enhance antitumour immunity. This concept is supported by the rapid emergence and clinical approval of ICBs therapies in multiple malignancies driven by diverse oncogenic signals. Indeed, ICBs’ ability to induce durable responses has revolutionised oncology during the past decade. Of note, several …

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  • Contributors SM and DGD wrote the manuscript.

  • Funding DGD’s work is supported by US NIH grants R01CA260872, R01CA260857, R01CA247441, and R03CA256764, and by the Department of Defence grants W81XWH-19-1-0284 and W81XWH-21-1-0738. SM receives funding through Overseas Research Fellowships from the Japan Society for the Promotion of Science (JSPS).

  • Competing interests DGD received consultant fees from Innocoll and preclinical research grants from Bayer, Exelixis, Surface Oncology and BMS.

  • Provenance and peer review Commissioned; externally peer reviewed.

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