CCA tumours, and particularly iCCAs and pCCAs, are characterized by a reactive desmoplastic stroma containing cancer-associated fibroblasts (CAFs) that crosstalk with CCA cells secreting paracrine factors such as heparin-binding EGF-like growth factor, stromal-cell derived factor 1 (SDF1), platelet-derived growth factor (PDGF)-B and extracellular matrix (ECM) proteins148. Here, HBEGF is linked to cancer.