Pregnancy Drug Uncovers New Insights into Brain Cancer Treatment

Hydralazine, a 70-year-old medication primarily used to treat high blood pressure, especially in pregnant women, has had its mechanism of action uncovered, revealing its potential in brain cancer treatment.

Researchers Kyosuke Shishikura and Megan Matthews from the University of Pennsylvania published their findings in Science Advances, showing that hydralazine blocks the oxygen-sensing enzyme 2-aminoethanethiol dioxygenase, or ADO.

This enzyme normally signals blood vessels to constrict in low oxygen conditions. By inhibiting ADO, hydralazine prevents this constriction, leading to vasodilation and reduced blood pressure. Matthews noted that preeclampsia, a condition affecting five to fifteen percent of pregnancies globally, particularly impacts Black mothers in the U.S., emphasizing the importance of safer treatments.

The study connected this hypertension mechanism to glioblastoma, a form of aggressive brain cancer, where ADO levels correlate with tumor aggressiveness. This discovery positions hydralazine as a potential means to induce cellular senescence in glioblastoma cells, effectively halting their growth without triggering inflammation or resistance, unlike traditional chemotherapy.

The collaboration involved structural biochemists from the University of Texas and neuroscientists from the University of Florida, who confirmed the drug's effects on brain cancer cells. The team plans to develop more specific ADO inhibitors that can effectively cross the blood-brain barrier, targeting tumor tissues while minimizing effects on healthy cells.

Matthews expressed hope for future discoveries linking established treatments to new solutions in medical challenges. This work received funding from several sources including the National Institutes of Health, the National Science Foundation, and the American Cancer Society, showcasing the collaborative effort to bridge maternal health and oncology.