Remarkably, such combinatorial treatment, constraining the activity of ET-1-driven p53/YAP/HIF-1α machinery contextually in tumor cells, EC and activated fibroblasts, induced a drastic reduction in the release of ET-1 and VEGF (Fig. 7A), and inhibited the compensatory signals that contributed to the PARPi escape pathway. Here, TP53 is linked to neoplasm.