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. The gene discussed is HIF1A; the disease is neoplasm.