Endothelin-1 (ET-1), a potent vasoconstrictor, was discovered in 1988. Its role in cardiovascular and pulmonary diseases has been widely investigated. Recent investigations of the pleiotropic actions of the endothelins, such as mitogenesis and inhibition of apoptosis, provide evidence for their potential role in cancer. Available data suggest that ET-1 plays a significant role in the growth and progression of such neoplasms as prostate and ovarian cancer, melanoma, bone malignancies, and other tumors. Development of endothelin receptor antagonists has allowed a better understanding of the role of ET-1 in cancer pathogenesis, and provided the possibility of therapeutic intervention. ET-1 exerts its action via the endothelin receptors A (ETA) and B (ETB); however, it appears that most of the mitogenic activity of ET-1 is mediated through the ETa receptor. Preliminary data from clinical trials investigating the ETa receptor antagonist, atrasentan, in patients with prostate cancer, were encouraging. The role of the endothelin axis in other malignancies is discussed as well.
American Journal of Cancer – Springer Journals
Published: Aug 9, 2012
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