EDN1 and cancer: In patients with bone metastases, a breakdown of the RANK pathway is observed, which causes an imbalance in the processes of resorption and bone formation as a result of a disequilibrium between RANK-L and OPG: when cancer cells reach bone, the release of growth factors such as fibroblast growth factors (FGFs), endothelin-1 (ET-1), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), transforming growth factor β (TGF-beta) and wingless-related integration site (WNT) is stimulated [118,119].