Based on the RNA-seq and TCGA data, as well as the analysis of patient-derived HG-SOC primary cultures, 3D cocultures, and orthotopic patient-derived xenografts (PDX), we report that repurposing macitentan, a dual ETAR/ETBR antagonist that is FDA-approved for treating pulmonary arterial hypertension [9], interferes with mutp53/YAP/HIF-1α hub-mediated tumor/stroma communication, and when combined with PARPi, elicits significant therapeutic efficacy in HG-SOC preclinical models. Here, EDNRB is linked to neoplasm.