Abstract

AbstractBackground and AimsDespite the impact of cutting‐edge technologies in providing deep molecular phenotyping of many tumours, management of cholangiocarcinoma (CCA), a rare and insufficiently studied cancer with marked heterogeneity (including intrahepatic and extrahepatic variants), has remained limited and it has poor prognosis. Renewed interest in this enigmatic disease has been fostered in the last decade. Here, we will give an overview of the most important gaps in knowledge of the basic and translational research of CCA that must be prioritized to improve the CCA management in the future.MethodsExploration was initially conducted on the Consensus Statement on Cholangiocarcinoma 2020, where after careful discussion of priorities, basic/translational research were selected and approved. Then, systematic literature searches using PubMed were performed by authors from different disciplines to highlight the most relevant areas requiring further study.ResultsGenetic and molecular characterization studies have identified the presence of actionable mutations in both intrahepatic (50%‐60%) and extrahepatic CCA (25%), but efficacy of targeted interventions is still hindered by several factors. They include a limited understanding of the intricate mechanisms of pharmacoresistance, the lack of accurate biomarkers enabling early detection of the disease, the complex role of the tumour microenvironment exerting both tumour‐promoting and tumour‐restraining functions, and the inadequacy of experimental models to recapitulate the wide heterogeneity of these tumours.ConclusionsPromoting international collaborations among scientists with multidisciplinary skills, and creation of platforms to collect data and biological samples of patients from different countries are the actions needed to understand better in this still challenging disease.

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