The therapeutic benefit of macitentan is to target not only HG-SOC cells expressing ETAR, but also to interfere with tumor microenvironmental elements (TME), such as fibroblasts, vascular, lymphatic, and immune cells, which mainly expressed ETBR3,4,36,65,66, representing a therapeutic strategy which may be used to design a targeted therapies towards TME elements and HG-SOC cells in combination with chemotherapeutics for cancer patients still suffering from limited treatment options. This evidence concerns the gene EDNRA and cancer.