Researchers at the University of Pennsylvania have uncovered a new mechanism for hydralazine, a common blood pressure drug, revealing its potential to slow the growth of glioblastoma, an aggressive brain cancer. The study, published in Science Advances, sheds light on how this decades-old medication works and points to possible new therapies for both preeclampsia and brain cancer.
Understanding hydralazine’s mechanism
Hydralazine has been used for over 70 years to lower high blood pressure. It acts as a vasodilator, widening blood vessels and improving blood flow. The drug is also widely prescribed for preeclampsia, a pregnancy-related high blood pressure condition that can threaten both the parent and baby if left untreated.
Despite its long history, scientists were unclear on how hydralazine worked at the molecular level. Understanding a drug’s mechanism can help explain side effects, identify patients who would benefit most, and reveal new therapeutic applications.
To investigate, researchers developed HYZyne, a modified version of hydralazine with a “tag” that allowed them to see which proteins the drug binds to inside cells. This approach highlighted a key enzyme called 2-aminoethanethiol dioxygenase (ADO), which detects oxygen and regulates proteins that relax blood vessels. By blocking ADO, hydralazine keeps blood vessels relaxed, lowering blood pressure.
Hydralazine’s potential in brain cancer treatment
Previous studies had linked ADO activity to glioblastoma growth. Researchers tested hydralazine on glioblastoma cells and observed that the cells entered senescence, a dormant state that dramatically slows growth without causing cell death. A single dose of hydralazine kept the cancer cells in this paused state for several days, suggesting that ADO-blocking drugs could become a new therapeutic approach.
Expert perspectives
Dr. Walavan Sivakumar, neurosurgeon and director at Providence Little Company of Mary, called the study “an elegant piece of science,” emphasizing that hydralazine exposes a new vulnerability in aggressive brain tumors. He noted that using the drug to induce dormancy represents a novel approach to brain cancer therapy.
Dr. Nicholas Klaiber, physician and Eastern Virginia Medical School graduate, described the research as “scientifically rigorous” but cautioned that continuous therapy would likely be needed to maintain tumor suppression, given glioblastoma’s high mutation rate.
Why this discovery matters
Hydralazine is inexpensive, widely available, and has decades of safety data, making it an attractive candidate for further research in neuro-oncology. While clinical application in glioblastoma patients is still in the future, the findings offer hope for low-cost, accessible treatments for a cancer with a 5-year survival rate of just 5%.
