Activation of ETAR by endothelin-1 is involved in tumor progression through angiogenesis, invasion, apoptosis, and the effect of the bone microenvironment.476,477 Activated ETAR signaling promotes osteoblast proliferation and new bone formation, which is highly associated with bone metastasis in PCa.478,479 Thus, the ETAR inhibitors zibotentan (ZD4054) and atrasentan have been tested in men with mCRPC. The gene discussed is EDNRA; the disease is neoplasm.