Researchers have uncovered a connection between elevated blood pressure and one of the most lethal forms of brain cancer, while also identifying a potential treatment avenue.
In the United States, approximately 120 million individuals are affected by high blood pressure, with around 6 million of them using a medication called hydralazine, marketed under the brand name Apresoline. This prescription drug, priced at $0.33 per pill, helps lower blood pressure by dilating blood vessels.
Now, a team from the University of Pennsylvania suggests that hydralazine, one of the oldest treatments for high blood pressure, may also be effective against glioblastoma. This aggressive brain cancer impacts roughly 12,000 people annually and results in a survival rate where half of those diagnosed succumb within 14 months.
Glioblastoma is characterized by its rapid growth within the brain, with a mere five percent of adult patients living beyond five years post-diagnosis. Notable figures, such as former Republican presidential candidate John McCain, who passed away from the disease in August 2018, highlight its severity; he died just 13 months after his diagnosis.
Scientists have discovered that glioblastoma flourishes in low-oxygen conditions, which it facilitates by impairing blood vessels to reduce oxygen supply to the tumor site.
However, laboratory experiments have indicated that hydralazine can counteract these low-oxygen conditions, effectively halting the proliferation of cancer cells and rendering them inactive.
The research is still in very early stages, and scientists say further tests are needed, although it is a potential sign of hope for victims of the disease.
Dr Megan Matthews, a chemist at the university who led the study, said: ‘It is rare that an old cardiovascular drug ends up teaching us something new about the brain.
Doctors say they have found a link between a common drug used to treat high blood pressure and brain cancer (stock image)
‘But that’s exactly what we’re hoping to find more of, unusual links that could spell new solutions.’
The study, published in the journal Science Advances, marked the first time that scientists had observed the mechanism by which hydralazine reduces blood pressure.
The medication has been available in the US for 70 years, but was approved at a time when it was not necessary to show how drugs work, only that they were effective.
In the study, scientists first conducted lab experiments that revealed hydralazine lowers blood pressure by binding to an oxygen-sensing enzyme called 2-aminoethanethiol dioxygenase (ADO).
This enzyme is activated when oxygen levels are low and works by breaking down a protein called regulators of G-protein signaling (RGS). That activation then causes blood vessel cells to constrict, resulting in elevated blood pressure.
ADO also works by maintaining certain proteins in the cell that allow it to survive low-oxygen conditions if the body isn’t receiving adequate oxygen due to any number of factors.
The scientists found that hydralazine blocked ADO, which caused the protein to build-up and triggered blood vessels to widen, lowering blood pressure.
In a separate experiment, the researchers then tested in the lab whether the drug could fight glioblastoma.
Former Republican presidential candidate John McCain, shown with vice presidential candidate Sarah Palin, died from glioblastoma in August 2018
Above shows hydralazine, a common blood pressure medication used in the US
Glioblastoma is a fast growing brain cancer that emerges in the brain. Patients generally do not survive beyond 14 months of their diagnosis (stock image)
In a lab test, the scientists found that hydralazine also blocked ADO in cancer cells, which caused a breakdown in proteins allowing the cell to thrive in low-oxygen conditions.
This triggered cellular ‘senescence’, or a dormant, non-dividing state in glioblastoma cells that effectively paused their growth.
The study could signal a potential new – and urgently needed – treatment for glioblastoma.
Doctors currently treat the cancer, which is typically diagnosed between the ages of 45 and 70 years, using surgery to remove the tumor, chemotherapy or radiation.
But the procedures normally only reduce symptoms of the disease or slightly prolong patients’ lives.
According to the Cleveland Clinic, only five percent of patients are still alive five years after their diagnosis.
Warning signs of the cancer include headaches, loss of appetite, memory problems, mood or personality changes, seizures, speech problems and changes in sensations. These symptoms normally appear suddenly in cases of the disease.
It is not clear what causes the cancer, but, in previous cases, it has been linked to previous exposure to radiation therapy and inherited genetic mutations.
Some scientists have investigated whether the cancer is linked to exposure to certain chemicals, although the results remain inconclusive.
