Endothelin receptor antagonists.
Hormone refractory prostate cancer remains true to its middle name: it is largely refractory to attempts to delay its progression. New targets and new therapies are demanded. Through a review of the available literature on endothelin and several preclinical observations, the endothelin axis has emerged as one such target. In phase II and III clinical trials of atrasentan, a potent and selective endothelin receptor A subtype (ET(A)) antagonist, disease progression was delayed in some men. This well tolerated, oral agent may help convert advanced prostate cancer to a more chronic disease. This review will discuss the endothelin axis, preclinical rationale and some of the available clinical trial data on this promising new approach.
Nelson
Joel B
JB
Department of Urology, University of Pittsburgh School of Medicine, 5200 Centre Ave, Suite 209, Pittsburgh, PA 15232, USA. nelsonjb@upmc.edu
D017209:Apoptosis / Q000187:drug effects; D000077868:Atrasentan; D014408:Biomarkers, Tumor / Q000378:metabolism; D002986:Clinical Trials as Topic; D018450:Disease Progression; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011759:Pyrrolidines / Q000627:therapeutic use*; D017466:Receptors, Endothelin / Q000378:metabolism; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D017466:Receptors, Endothelin; D000077868:Atrasentan