Old Blood Pressure Drug May Hold the Key to Halt Aggressive Brain Cancer Growth
A 70-year-old medical mystery around a critical blood-pressure medication, hydralazine, was finally solved. Not only do scientists now understand how it works on a molecular level — which offers important clues to help improve the drug chemically for patients with hypertension disorders or for treating preeclampsia during pregnancy — it also holds potential to stop brain tumors from growing.
A collaboration between universities across the U.S. outlines in a study published in Science Advances how cells from the most aggressive form of brain cancer treated with hydralazine became dormant. This shows that sometimes, instead of inventing novel treatments from scratch, we just have to look at what we already have from a different angle.
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Medications’ Mechanisms of Action Often Not Understood
As one of the World Health Organization’s most essential medications, hydralazine entered the market 70 years ago to treat high blood pressure and preeclampsia, a pregnancy-related blood pressure condition that causes around 10 percent of maternal deaths worldwide, according to the World Health Organization.
Despite its success, researchers didn’t really know how hydralazine worked its magic — and it’s not alone. Prior to the 1980s, many drugs were approved solely based on clinical observation, and only later did scientists “try to explain the biology behind it,” said Kyosuke Shishikura, a physician-scientist at the University of Pennsylvania, in a press statement.
In their study, the research team finally identified what hydralazine targets at the molecular level. They found that it blocks an oxygen-sensing enzyme called 2-aminoethanethiol dioxygenase (ADO), which normally signals blood vessels to constrict depending on oxygen levels, causing blood pressure to rise.
Hydralazine Stops Aggressive Brain Cancer From Growing
But how does brain cancer come into play? Cancer researchers have long suspected that ADO plays an important role in one of the most aggressive forms of brain cancer, glioblastoma, because of its low-oxygen environment. ADO levels seem to rise the more aggressive the tumor becomes, but no effective ADO inhibitor has been known to confirm the theory.
Using a high-resolution imaging technique called X-ray crystallography, biochemists from the University of Texas were able to show that hydralazine interacts with ADO, leading to further tests on brain cancer cells. In vitro, hydralazine treatment caused tumor cells to enter senescence — a dormant state where cells stop growing. Compared to chemotherapy, this approach works more selectively, potentially causing fewer side effects.
Improving an Old Cardiovascular Drug
Finally, having the biochemical mechanism uncovered doesn’t just benefit new treatment options but also allows researchers to fine-tune hydralazine for its original use: treating high blood pressure.
“Understanding how hydralazine works at the molecular level offers a path toward safer, more selective treatments for pregnancy-related hypertension — potentially improving outcomes for patients who are at greatest risk,” explained Shishikura.
Discoveries like this inspire scientists to reconsider long-established treatments that might have surprising therapeutic potential for other medical challenges. The next steps are refining the chemistry to design safer, more specific, and effective ADO inhibitors that can cross the blood-brain barrier to reach their target.
“It’s rare that an old cardiovascular drug ends up teaching us something new about the brain,” said study co-author Megan Matthews, assistant professor at the University of Pennsylvania, in the news release, “but that’s exactly what we’re hoping to find more of — unusual links that could spell new solutions.”
This article is not offering medical advice and should be used for informational purposes only.
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