Endothelin inhibition: Novel therapy for prostate cancer

Purpose: 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 ETA and ETB), preclinical studies of its role in prostate cancer, results of phases I and II clinical trials, and future directions are reviewed. Materials and 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 ETA 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.