Endothelin receptor antagonists: rationale, clinical development, and role in prostate cancer therapeutics.

The endothelins (ETs), which include ET-1, ET-2, ET-3, and their receptors ET-A and ET-B, play a major role in tumor growth, proliferation, apoptosis, angiogenesis, and bone metastasis. Atrasentan is a novel and selective inhibitor of ET-1 and ET-A. In vitro and in vivo data show that this oral agent is capable of inhibiting tumor cells in vitro. More recently, this agent was studied in several phase I trials with refractory carcinoma patients. Subsequently, phase II and III clinical trials evaluating atrasentan in patients with hormone-refractory prostate carcinoma have suggested that targeting this pathway may be a new therapeutic strategy in the treatment of solid malignancies, specifically, prostate cancer.