Endothelin inhibition: novel therapy for prostate cancer.
OBJECTIVE
Androgen refractory prostate cancer continues to evade effective treatment. The potent vasoconstrictor endothelin-1 is produced by prostate cancer and appears to have a role in prostate cancer progression and morbidity. Background on the endothelin axis (endothelin-1 and endothelin receptors ET(A) and ET(B)), preclinical studies of its role in prostate cancer, results of phases I and II clinical trials, and future directions are reviewed.


METHODS
A review was conducted of the published data on the endothelin axis in prostate cancer.


RESULTS
Based on preclinical and clinical trial data, the endothelin axis is emerging as potentially important in the biology of prostate cancer progression and morbidity. Drugs targeting the endothelin axis, such as the potent ET(A) receptor antagonist atrasentan (ABT-627), have been studied in large clinical trials and appear to have an impact on disease progression and morbidity.


CONCLUSIONS
The role of the endothelin axis in prostate cancer deserves further investigation in the laboratory and clinic. This new strategy for intervention is promising.
Nelson
Joel B
JB
Department of Urology, University of Pittsburgh School of Medicine, Pennsylvania 15232, USA. nelsonjb@msx.upmc.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077868:Atrasentan; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011759:Pyrrolidines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019332:Endothelin-1; D011759:Pyrrolidines; D000077868:Atrasentan