In this context, it has been shown that PCa promotes osteoblastic lesions that via endothelin 1 (ET-1) signaling, which stimulates osteoblasts via the EAR. Pharmacological targeting of ET-1 signaling has shown considerable promise in mouse models of breast cancer, resulting in decreased tumor burden and metastatic lesions [121]. The gene discussed is EDN1; the disease is breast carcinoma.