title: Endothelin receptor antagonists: rationale, clinical development, and role in prostate cancer therapeutics.
abstract: 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.
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Center, The Cleveland Clinic Foundation, 9500 Euclid Avenue, R-35, Cleveland, OH 44195, USA. choueit@ccf.org
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Thakkar
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Garcia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077868:Atrasentan; D002986:Clinical Trials as Topic; D018450:Disease Progression; D065130:Endothelin A Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D016232:Endothelins / Q000502:physiology*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D044022:Receptor, Endothelin A / Q000502:physiology; D017466:Receptors, Endothelin / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D065130:Endothelin A Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D000077868:Atrasentan