An Old Blood Pressure Drug Shows New Promise Against Aggressive Brain Cancer

One of the world’s oldest and most widely prescribed blood pressure medications may hold unexpected potential in the fight against one of the deadliest forms of brain cancer. Researchers at the University of Pennsylvania, led by Dr. Megan Matthews and Dr. Kyosuke Shishikura, have reported that hydralazine—a drug introduced into clinical use more than half a century ago—can halt the growth of aggressive brain tumors known as glioblastomas. Their findings, published in Science Advances in November 2025, point to a novel and promising therapeutic strategy that does not rely on killing cancer cells outright, but instead forces them into a permanent growth arrest.

In laboratory experiments, the research team treated human glioblastoma cells with hydralazine and observed dramatic effects within just three days. Rather than continuing to divide rapidly, as glioblastoma cells typically do, the treated cells entered a state known as cellular senescence. Senescent cells remain alive but lose their ability to replicate, effectively stopping tumor expansion. This approach is particularly intriguing because glioblastoma is notoriously resistant to conventional treatments such as chemotherapy and radiation, which aim to destroy cancer cells but often damage healthy brain tissue in the process (National Cancer Institute; The Lancet Oncology).

To understand how hydralazine exerts this effect, the Penn-led team investigated its molecular mechanism of action. They discovered that the drug directly inhibits an oxygen-sensing enzyme called 2-aminoethanethiol dioxygenase (ADO). This enzyme plays a key role in helping cells adapt to low-oxygen, or hypoxic, environments—a condition commonly found inside fast-growing tumors. Using X-ray crystallography in collaboration with scientists at the University of Texas, the researchers demonstrated that hydralazine binds to the metal center of the ADO enzyme, effectively blocking its activity and disrupting the tumor cells’ ability to sense and respond to oxygen deprivation.

This mechanism is especially significant because hypoxia is a hallmark of glioblastoma and contributes to its aggressiveness and resistance to therapy. Cancer cells that thrive in low-oxygen conditions are often more invasive and harder to eliminate. By disabling the ADO pathway, hydralazine appears to strip glioblastoma cells of a critical survival advantage. Similar oxygen-sensing pathways have been studied extensively in cancer biology, particularly in relation to hypoxia-inducible factors (HIFs), which are known to drive tumor progression (Nature Reviews Cancer; Cell).

Further experiments, conducted in partnership with neuroscientists at the University of Florida, revealed an unexpected connection between brain cancer and preeclampsia, a dangerous pregnancy-related condition characterized by high blood pressure and impaired oxygen signaling in the placenta. The researchers found that shutting down the same oxygen-sensing pathway affected both conditions, suggesting a shared underlying biological mechanism. This surprising overlap highlights how insights from one area of medicine can inform breakthroughs in another (American Heart Association; Nature Medicine).

The implications of this discovery are far-reaching. Because hydralazine is already approved by regulatory agencies such as the U.S. Food and Drug Administration and has a long history of clinical use, repurposing it for brain cancer treatment could significantly shorten the path to clinical trials. Drug repurposing has increasingly been recognized as a cost-effective and time-efficient strategy in oncology research (World Health Organization; Science Translational Medicine).

While more studies are needed to confirm these findings in animal models and human patients, the research offers new hope against a cancer that currently has a very poor prognosis. It also underscores a broader lesson in biomedical science: even well-known, decades-old drugs can reveal powerful new applications when examined through the lens of modern molecular biology.