Many of the soluble factors, including cyto/chemokines (e.g., IL-6), growth factors (e.g., PDGF) and morphogens (e.g., Wnt/β-catenin, Hippo, Notch and Hh), are also relevant for the development of a chemoresistant phenotype, either by providing CCA cells with tools to escape from drug-induced apoptosis or by expanding the CSC compartment. This evidence concerns the gene IL6 and cholangiocarcinoma.