EDN1 and cancer: In view of the IH-induced increase of endothelin-1 secretion by 4T1 cells, we used macitentan, a dual endothelin receptor antagonist with enhanced tissue penetration and receptor binding properties and superior oral efficacy in animal models40,41, as a pharmacological tool to assess the role of ET-1 in the initiation and development of cancer in response to intermittent hypoxia.