Endothelin Receptors as Therapeutic Targets in Castration-Resistant Prostate Cancer

Context: New, effective therapies for castration-resistant prostate cancer (CRPC) are needed to treat this lethal form of the disease. Through an understanding of the biology of endothelin-1 (ET-1) and the endothelin receptors (the endothelin axis) in prostate cancer (PCa), this axis has emerged as a promising target for therapeutic intervention. Objectives: This review discusses the biology of the endothelin axis, several of the preclinical observations supporting the therapeutic rationale, and some of the available clinical trial data on this promising new approach. Evidence acquisition: A nonsystematic review of the literature, including PubMed and congress abstracts, was performed in 2008. Evidence synthesis: Based on the clinical trial results, the limitations and promise of the endothelin axis as a therapeutic target is discussed. Conclusions: Clinical trials of potent, selective, or specific endothelin A (ETA) receptor subtype antagonists have demonstrated clinical activity. Such agents have not yet been approved for the treatment of PCa, but the ongoing phase 3 trials will further define their efficacy for treating CRPC. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.