Fast-Growing Cancer Could Be Slowed by Common Blood Pressure Drug, Research Shows

Scientists studying a decades-old blood pressure medication have accidentally discovered its potential as a cancer treatment, potentially opening a new front in the battle against aggressive brain tumors.

Hydralazine, a medication used to treat high blood pressure since the 1950s, has been found to directly target an enzyme crucial for cancer cell survival. The discovery was made by a research team at the University of Pennsylvania, who were investigating the drug’s mechanisms.

“It came from a ‘pre-target’ era of drug discovery, when researchers relied on what they saw in patients first and only later tried to explain the biology behind it,” explained Kyosuke Shishikura, a physician-scientist involved in the study.

The team discovered that hydralazine works by targeting a small but vital enzyme called 2-aminoethanethiol dioxygenase (ADO). This enzyme functions as a cellular oxygen sensor, helping cells survive when oxygen levels are low – a condition common in rapidly growing tumors like glioblastoma, an aggressive form of brain cancer with notoriously poor treatment outcomes.

In fast-growing cancers, tumor cells multiply so quickly that their blood supply cannot keep pace, creating oxygen-deprived regions within the tumor. While normal cells die in low-oxygen environments, cancer cells activate special survival mechanisms that allow them to continue dividing even when starved of oxygen. The ADO enzyme plays a key role in this process.

“ADO is like an alarm bell that rings the moment oxygen starts to fall,” said Megan Matthews, an assistant professor in Penn’s Department of Chemistry and researcher on the study.

Using advanced techniques including X-ray crystallography, the researchers determined that hydralazine binds to ADO and effectively silences this alarm system. By inhibiting the enzyme, the drug shuts down the cell’s oxygen response system and forces cancer cells to stop dividing.

To test this discovery, the team treated human glioblastoma cells with hydralazine in laboratory conditions. After just three days, they observed that the treated cancer cells had stopped multiplying and had physically changed, becoming larger and flatter. The cells had entered a state called “senescence” – essentially a permanent growth arrest or cellular “sleep mode.”

While the drug didn’t kill the cancer cells outright, it removed their ability to grow and spread – a significant development for treating aggressive cancers like glioblastoma, which typically resist conventional treatments and frequently recur after surgery and chemotherapy.

This repurposing discovery is particularly promising because hydralazine already has FDA approval for its blood pressure indication. This established safety profile could potentially accelerate its path to clinical use for cancer treatment compared to developing an entirely new drug.

The pharmaceutical industry has increasingly focused on drug repurposing as a cost-effective strategy for expanding treatment options. Finding new uses for existing medications can significantly reduce development costs and timeline, as safety profiles and manufacturing processes are already established.

However, the researchers caution that their work represents only the first step in a longer development process. The experiments thus far have been limited to cell cultures, and have not yet been tested in animal models or human subjects.

“The next critical phase will involve testing whether ADO can be safely and effectively blocked in living systems,” noted the researchers. Moving from laboratory success to clinical application will require additional studies to determine optimal dosing, delivery methods, and potential combination strategies with existing cancer treatments.

“Understanding how hydralazine works at the molecular level offers a path toward safer, more selective treatments,” Matthews emphasized. This molecular understanding could potentially lead to the development of more targeted therapies that specifically inhibit ADO with fewer side effects.

For patients with aggressive cancers like glioblastoma, where treatment options remain limited and survival rates low, this accidental discovery represents a potential new avenue of hope in what has historically been a challenging therapeutic landscape.