A decades-old drug, hydralazine, traditionally used to treathigh blood pressureandpreeclampsiaduringpregnancy, is now showing promise in fighting aggressivebrain tumors. Scientists at the University of Pennsylvania discovered its molecular mechanism, revealing that hydralazine targets an enzyme called 2-aminoethanethiol dioxygenase (ADO), which acts as an oxygen sensor controlling blood vessel constriction. The findings of the research are published in Science Advances. Hydralazine lowers blood pressure by directly relaxing the smooth muscles in the walls of small arteries (arterioles). It interferes with calcium metabolism in vascular smooth muscle, reducing intracellular calcium levels. This relaxation causes the blood vessels to dilate, decreasing peripheral resistance and allowing blood to flow more easily. This vasodilation reduces blood pressure and decreases the workload on the heart. Because hydralazine stimulates the sympathetic nervous system, it is often prescribed with a beta-blocker to prevent rapid heart rate as a side effect. By binding to and inhibiting ADO, hydralazine “silences” this oxygen alarm, preventing blood vessels from tightening and lowering blood pressure. Remarkably, this action also disrupts a survival mechanism in glioblastoma cells, the most aggressive brain tumors, causing them to enter a dormant state and halting their growth without triggering harmful inflammation or resistance. Using advanced techniques like X-ray crystallography and tumor cell testing, the researchers detailed how hydralazine’s interaction with ADO provides a direct link between hypertensive disorders and brain cancer biology. This discovery not only enhances understanding of hydralazine’s longstanding use in maternal health but also opens a new therapeutic avenue for designing safer, targeted brain cancer treatments. While hydralazine is an established drug for managing pregnancy-related hypertension, these findings could lead to repurposing it as part of brain cancer therapy, potentially improving outcomes for patients with few options. Researchers emphasize the importance of further studies to develop optimized versions of hydralazine that maximize anticancer effects while maintaining safety. This breakthrough exemplifies how revisiting well-known medications can uncover unexpected benefits, highlighting the potential of drug repurposing to accelerate new treatments for challenging diseases. REFERENCE:Kyosuke Shishikura et al. ,Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.Sci. Adv.11,eadx7687(2025).DOI:10.1126/sciadv.adx7687