A decades-old blood pressure drug may hold new promise in slowing the growth of one of the deadliest cancers, according to new research from the University of Pennsylvania.
Scientists discovered that hydralazine, an FDA-approved medication introduced in the 1950s to treat hypertension, can interfere with a key survival mechanism used by cancer cells when oxygen levels drop. The findings, recently released by the university, highlight hydralazine’s previously unknown effect on an enzyme that helps cancer cells adapt and proliferate in low-oxygen environments.
The research team, led by physician-scientist Dr. Kyosuke Shishikura and chemistry professor Dr. Megan Matthews, found that hydralazine directly targets an enzyme called 2-aminoethanethiol dioxygenase (ADO). This enzyme acts as a cellular oxygen sensor, allowing rapidly growing tumors—such as glioblastoma—to survive when their blood supply cannot meet their oxygen demands.
“ADO is like an alarm bell that rings the moment oxygen starts to fall,” Matthews said in the release. “Hydralazine silences that alarm.”
Using X-ray crystallography and other molecular imaging techniques, the team showed that hydralazine binds to ADO and stops it from functioning. Without this enzyme, tumor cells lose their ability to survive in low oxygen and can no longer divide normally.
In laboratory experiments using human glioblastoma cells, hydralazine treatment halted cell growth within three days. The cells entered a state known as senescence, or permanent dormancy, in which they stopped dividing but were not destroyed. While this effect does not eliminate cancer cells, it could slow tumor progression and potentially improve outcomes when combined with other therapies.
Glioblastoma, an aggressive brain cancer with a high relapse rate, remains one of the most difficult malignancies to treat. Current therapies—including surgery, radiation, and chemotherapy—offer limited survival benefits. Because hydralazine is already approved for cardiovascular use, researchers say it could be repurposed for oncology more quickly than new investigational drugs.
The study’s authors caution that these results are preliminary. Tests so far have been limited to cell cultures, not animals or human subjects. Future research will aim to determine whether blocking ADO can safely and effectively suppress tumor growth in living systems.
“Understanding how hydralazine works at the molecular level offers a path toward safer, more selective treatments,” Matthews said. The researchers emphasize that this discovery marks an early step toward potential cancer repurposing—not an immediate clinical therapy.
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