EGFR and cholangiocarcinoma: One of the most significant signalling pathways between CCA cells and CAFs is the HBEGF/EGFR signalling pathway, in which there is an intense two-way communication by which CCA cells activate CAFs and, in turn, CAFs sustain the invasive phenotype of cancer cells; activation of EGFR triggers TGF-β1 production by CCA cells, further enhancing fibroblast activation and CAF synthesis of HBEGF (Claperon et al., 2013).