unexpected Hope for Glioblastoma: Repurposing a Long-Standing Blood Pressure Medication
A decades-old drug used to treat high blood pressure, hydralazine, is showing promise as a potential therapy for the aggressive brain cancer glioblastoma. Research from the University of Pennsylvania, published October 15, 2025 in Science Advances, reveals a surprising connection between blood pressure regulation and tumor growth, centering on the enzyme 2-aminoethanethiol dioxygenase (ADO).
Approximately 17 million adults in France – roughly one in three – live with high blood pressure, with nearly 6 million unaware of thier condition. Hydralazine, a vasodilator that relaxes blood vessels, has been a mainstay in hypertension treatment for years and remains a preferred option for severe hypertension during pregnancy. The new research delves into how hydralazine works, uncovering a potential secondary benefit.
The study identifies ADO as a critical target. ADO functions as an oxygen sensor within blood vessels, triggering constriction when oxygen levels drop. “ADO acts like an alarm bell that goes off as soon as oxygen levels start to drop,” explains scientist Megan Matthews. Unlike typical cellular processes requiring time-consuming DNA and RNA replication, ADO initiates a rapid biochemical response, essentially flipping a switch within seconds. Researchers found that hydralazine binds to and blocks ADO, preventing this constriction and keeping vessels dilated.
This mechanism is especially relevant to glioblastoma, the most common and aggressive form of brain cancer in adults. Previous research had already established a link between elevated levels of ADO and more aggressive tumor behavior, suggesting that inhibiting the enzyme could perhaps slow cancer progression.
In laboratory experiments using glioblastoma cells, the team demonstrated that blocking ADO with hydralazine induced senescence – a state where cancer cells stop dividing. this effectively slowed tumor growth in vitro by disrupting the cancer cells’ ability to thrive in low-oxygen environments, where they typically flourish. The research highlights the ability to prevent ADO’s “alarm signal” in these oxygen-deprived conditions.
While these findings are highly encouraging, it’s crucial to note they are preclinical. The research currently focuses on cells studied in a laboratory setting.The next steps involve designing more specific ADO inhibitors tailored to target tumor tissues, with the ultimate goal of developing a more effective treatment for glioblastoma.
Even though hydralazine is not currently a frist-line treatment for hypertension outside of pregnancy due to potential cardiac side effects, the study underscores a essential biological principle and opens the door to therapeutic repositioning focused on the ADO enzyme. Further, larger-scale testing is required to validate these initial findings and determine the potential for clinical request.
