A medication that has been prescribed for high blood pressure for more than seven decades may hold surprising new potential in the fight against one of the deadliest forms of brain cancer.
Hydralazine, a widely used vasodilator first approved in the mid-20th century, has long been an important treatment for hypertension and preeclampsia.
Yet despite its extensive medical use, its precise biological mechanism has remained a mystery – until now.
A new study from researchers at the University of Pennsylvania has finally revealed how hydralazine works at the molecular level and, unexpectedly, uncovered evidence that the drug may slow the growth of glioblastoma, a fast-spreading and notoriously difficult-to-treat brain tumor.
Their work, published in Science Advances, provides new scientific clarity about a familiar medication and opens pathways for future brain cancer therapies.
Decoding a decades-old medical mystery
Hydralazine has long been known to lower blood pressure by widening blood vessels and improving circulation.
It is frequently given to patients with preeclampsia, a potentially life-threatening pregnancy-related condition, and remains accessible worldwide due to its low cost. Nevertheless, researchers were never fully certain how the drug triggered these effects inside the body.
To answer that question, the University of Pennsylvania research team engineered a modified form of the drug called HYZyne, designed to act like hydralazine but with a biological βtagβ attached.
This allowed scientists to observe which proteins HYZyne and, therefore, hydralazine bound to inside cells. Out of the few proteins the probe identified, one enzyme clearly stood out: 2-aminoethanethiol dioxygenase (ADO).
ADO plays a key role in detecting oxygen levels and regulating blood vessel relaxation. The study revealed that hydralazine works by disabling this enzyme, keeping blood vessels relaxed and ultimately lowering blood pressure.
This long-awaited discovery not only finally explains hydralazineβs clinical effect, but also suggests new medical applications far beyond hypertension alone.
From blood pressure management to potential cancer therapy
With ADO now confirmed as hydralazineβs primary target, researchers turned to diseases linked to the same enzyme, including glioblastoma.
Current treatment options for this aggressive cancer are limited to surgery, radiation, and chemotherapy, and survival outcomes remain devastatingly poor.
Most patients survive only 12β18 months after diagnosis, and long-term survival beyond five years is rare.
Previous scientific work has shown that glioblastoma cells rely heavily on ADO activity to thrive.
When the Penn research team treated these cancer cells with hydralazine, they observed a striking effect: instead of continuing to multiply, the tumors entered senescence – a dormant, non-dividing state.
While the process did not kill cancer cells outright, it significantly slowed their growth, with a single treatment halting activity for several days.
The results are preliminary and still limited to laboratory models, but they suggest the possibility that hydralazine or new ADO-targeting drugs could one day be incorporated into glioblastoma therapy.
Experts cautiously optimistic
Medical professionals not involved with the study have praised its scientific depth while urging caution about clinical implications.
Walavan Sivakumar, MD, a neurosurgeon and director of neurosurgery at Providence Little Company of Mary, described the findings as βa very elegant piece of science,β noting that the study not only solved a historical pharmacological puzzle but also exposed a new vulnerability in brain tumors.
He emphasized that pushing cancer cells into a dormant βsleep stateβ represents a fundamentally different therapeutic strategy.
Sivakumar also highlighted a major advantage: hydralazine is inexpensive, widely available, and backed by decades of safety data – something rare in neuro-oncology, where drugs are often costly and harsh.
βThe idea that a low-cost, generic medication might help slow a tumor like glioblastoma is extremely attractive,β he said.
However, experts also warn that long-term practicality remains uncertain. Nicholas Klaiber, MD, called the study βcompelling,β but noted that keeping tumors in senescence may require continuous treatment.
He also cautioned that glioblastoma mutates rapidly and may eventually become resistant to hydralazine by increasing ADO production.
A promising lead, but more research ahead
The discovery marks a significant scientific milestone both as the first clear explanation of how hydralazine works and as a potential step toward new, more accessible treatments for brain cancer.
While clinical application remains years away, the study lays the groundwork for future trials and fuels hope for improved outcomes in one of medicineβs most challenging cancers.
A familiar drug may soon serve an unfamiliar role – not just controlling blood pressure, but possibly slowing one of the deadliest tumors known to medicine.
