From Fox News: Scientists studying an existing blood pressure drug called hydralazine accidentally discovered that it could potentially fight cancer.
Hydralazine has been used to treat high blood pressure since the 1950s, but until now it’s been unclear exactly how it works.
“It came from a ‘pre-target’ era of drug discovery, when researchers relied on what they saw in patients first and only later tried to explain the biology behind it,” Kyosuke Shishikura, a physician-scientist at the University of Pennsylvania who was involved in the study, said in a press release from the university.
Shishikura and a wider research team uncovered that hydralazine directly targets a small but crucial enzyme called 2-aminoethanethiol dioxygenase (ADO).
This enzyme acts like a cellular oxygen sensor, helping cells survive when oxygen levels are low. This can help enable fast-growing tumors like glioblastoma, an aggressive form of brain cancer that resists treatment and almost always comes back.
Below are excerpts from a press release published by Penn Today:
In a paper published in Science Advances, the team uncovered the method of action of hydralazine, and in doing so, revealed an unexpected biological link between hypertensive disorders and brain cancer. The findings highlight how long-established treatments can reveal new therapeutic potential and could help in the design of safer, more effective drugs for both maternal health and brain cancer.
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The team found that hydralazine blocks an oxygen-sensing enzyme called 2-aminoethanethiol dioxygenase (ADO)—a molecular switch that tells blood vessels when to tighten.
“ADO is like an alarm bell that rings the moment oxygen starts to fall,” Matthews says. “Most systems in the body take time; they have to copy DNA, make RNA, and build new proteins. ADO skips all that. It flips a biochemical switch in seconds.”
Hydralazine acts by binding to and blocking ADO, which means it effectively “mutes” that oxygen alarm. Once the enzyme was silenced, the signaling proteins it normally degrades—called regulators of G-protein signaling (RGS)—remained stable.
The buildup of RGS proteins, says Shishikura, tells the blood vessels to stop constricting, effectively overriding the “squeeze” signal. This reduces intracellular calcium levels, which he calls the “master regulator of vascular tension.” As calcium levels fall, the smooth muscles in blood vessel walls relax, causing vasodilation and a drop in blood pressure.
READ MORE from Fox News.
Hydralazine, a decades-old blood pressure medication, has been shown to block an oxygen-sensing enzyme, halting the growth of aggressive brain tumors by inducing cellular dormancy. @Penn @ScienceAdvances https://t.co/FJWiUsHZZ6 https://t.co/X02GpCWtxp
— Medical Xpress (@medical_xpress) November 16, 2025
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