Hydralazine: Decades-Old Blood Pressure Drug Shows Promise Against Brain Cancer
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A long-used medication for hypertension, hydralazine, is revealing a surprising new potential: fighting aggressive brain cancers. New research published in Science Advances in July 2025, details how the drug impacts a key enzyme linked to both high blood pressure and the growth of glioblastoma tumors.
For decades, hydralazine has been a mainstay in treating high blood pressure, particularly in cases of preeclampsia, a perilous hypertensive disorder affecting 5-15% of maternal deaths globally. Yet, the precise mechanisms behind its effectiveness have remained elusive – until now. Researchers at the University of Pennsylvania have discovered that hydralazine works by blocking the enzyme 2-aminoethanethiol dioxygenase (ADO).
This discovery is meaningful because ADO is also implicated in the growth of glioblastoma, one of the most aggressive and challenging-to-treat forms of brain cancer.”Hydralazine is one of the earliest vasodilators ever developed, and it’s still a first-line treatment for preeclampsia,” explains a physician-scientist from the University of Pennsylvania.”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.”
The Role of ADO in Cancer and Hypertension
The research team found that ADO catalyzes reactions that produce hypotaurine, a chemical that fuels cancer growth. They describe ADO as an “alarm bell” triggered by dropping oxygen levels, initiating a cascade that constricts blood vessels by dismantling RGS proteins (regulators of G-protein signaling). Previous studies have indicated that glioblastoma tumors often exploit ADO, utilizing it to generate hypotaurine, which enhances cancer cell proliferation, survival, and stress tolerance.
Crucially, before this study, no known inhibitors of ADO existed. Hydralazine, though, effectively silences ADO, preventing the attack on RGS proteins, relaxing blood vessels, and lowering blood pressure. In laboratory experiments using human glioblastoma cells, hydralazine demonstrably halted tumor growth by blocking ADO’s activity.
From Blood Pressure to Brain Tumors: A New Therapeutic Avenue
While these findings are preliminary – clinical trials are needed to confirm hydralazine’s efficacy in glioblastoma patients – they offer a promising new direction for cancer treatment. The newfound understanding of hydralazine’s mechanism also sheds light on its effectiveness in treating preeclampsia, potentially leading to more refined and personalized treatment strategies.
“Understanding how hydralazine works at the molecular level offers a path toward safer, more selective treatments for pregnancy-related hypertension – potentially improving outcomes for patients who are at greatest risk,” notes a chemist from the University of Pennsylvania.The ability to target ADO could allow for the development of drugs that specifically disrupt cancer cell defenses, while minimizing harm to healthy tissues.
The widespread use of hydralazine provides a significant advantage. As the drug is already approved and readily available, scientists have a head start in developing new treatments based on its mechanism of action. Further research could focus on refining hydralazine or creating new compounds that more effectively inhibit ADO, potentially adding another weapon to the arsenal against glioblastoma.
“It’s rare that an old cardiovascular drug ends up teaching us something new about the brain,” says a researcher involved in the study, “but that’s exactly what we’re hoping to find more of – unusual links that could spell new solutions.” This discovery underscores the potential for repurposing existing drugs to address previously unrelated diseases, opening up exciting new avenues for medical innovation.
