2020 Year in Review: Cholangiocarcinoma

As a result of the COVID-19 pandemic, year 2020 has witnessed unprecedented changes in the practice of medicine. The effect on medical conferences has been equally dramatic, and several major meetings have been canceled or altered. Fortunately, the oncology community adapted quickly!
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Meta-analysis identifies upregulation of several novel genes that have not been previously described, and suggests the potential role of ERBB2 and extracellular genes in the pathogenesis of CCA.
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Interim analysis of the part 2 dose-expansion portion of an ongoing 2-part phase 1 Japanese study shows that the FGFR1 tyrosine kinase inhibitor E7090 was active with a manageable safety profile in CCA patients with FGFR2 gene fusion.
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AKT and NOTCH intracellular domain (NICD) targets YAP and SOX9 might be potential targets for therapeutic intervention in intrahepatic CCA subsets, while cholestatic injury or NASH might induce hepatocyte-to-cholangiocyte reprogramming that increases risk of intrahepatic CCA.
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Preliminary results of a phase 2 study suggest that the addition of the PI3K inhibitor copanlisib to chemotherapy in the first-line setting was not associated with survival benefit in patients with advanced CCA.
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Preclinical data implicate the ELR+ chemokine/CXCR2 axes in the pathogenesis of CCA, warranting further studies to define its role in CCA.
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Molecular analyses of biliary tract cancers indicate that neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare, suggesting that it is not a major driver of BTC pathogenesis.
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Data reported at the ASCO 2020 GI Cancers Symposium indicate that treatment with neoadjuvant definitive chemoradiation followed by orthotopic liver transplantation was associated with better outcomes compared with definitive chemoradiation alone in patients with unresectable extrahepatic/hilar CCA.
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Preclinical evidence using an genetically engineered mouse model of IDH1-mutated intrahepatic CCA indicates that the selective IDH1 inhibitor ivosidenib mediates its antitumor activity by promoting hepatic progenitor-cell differentiation, and inducing T-cell–mediated antitumor immune response.
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First results of the multicohort phase 2 LEAP-005 study suggest that lenvatinib plus pembrolizumab combination immunotherapy has promising antitumor activity in patients with biliary tract cancer.
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