Given that the tumor-promoting TME phenotype is mediated via diverse mechanisms, we identified the ET-1R-mediated p53/YAP/HIF-1α hub as a therapeutic vulnerability that impacts the secretome of HG-SOC cells and the crosstalk between tumor cells with EC and activated fibroblasts, thus regulating the DNA damage response and the efficacy of PARPi treatment. This evidence concerns the gene TP53 and neoplasm.