Cholangiocarcinoma (CCA), the second most prevalent liver cancer, encompasses a heterogenous group of bile duct malignancies. It predominantly arises from the epithelial cells lining the bile ducts termed cholangiocytes. Most CCA are highly desmoplastic adenocarcinomas, enmeshed in a tumour immune microenvironment. It exhibits a poor prognosis owing to its invasiveness and therapeutic resistance. Based on the anatomical location, CCA is classified into intrahepatic CCA (iCCA), perihilar CCA (pCCA) and distal CCA (dCCA). The epidemiology of these cancers varies worldwide. Infections with specific species of trematodes (flatworm parasites, commonly called flukes) are a major cause of CCA in regions where liver fluke infection is endemic. Moreover, iCCA can be further subdivided according to its morphology and cellular origin.1 2 The molecular heterogeneity of CCA reflects these differences. It displays genomic alterations in various pathways involved in cell cycle regulation, genomic stability and, notably, epigenetic modulation and chromatin remodelling, accompanied by considerable variation in the transcriptomic, methylomic, microRNA and proteomic levels. Jusakul et al performed a large-scale, integrative, multi-omics analysis and identified four prognostic clusters (Jusakul-Clusters) of CCA.3 Two of these were enriched for pCCA and dCCA, and one of them comprised exclusively of fluke-associated tumours. The cluster with the best prognosis consisted mainly of iCCA tumours, and was characterised by FGFR fusions, IDH1/2 …