TGFB1 and neoplasm: Beyond the effects of molecular alterations within biliary tract tumor cells themselves, these malignant cells also secrete PDGF-D that helps to recruit large numbers of CAFs to the tumor environment through PDGFR-β signaling [21], while the malignant production of FGF, PDGF, and TGF-β maintains the CAFs in a persistently activated state [22], ultimately producing the desmoplastic stromal reaction characteristic of BTCs.