How antidepressants could help treat brain tumors

When you think of antidepressants, treating aggressive brain tumors might not be the first thing that comes to mind, as these medications are typically associated with mental health conditions like depression or anxiety.

Yet, a recent study led by Switzerland’s renowned ETH Zurich has uncovered a unique and hopeful approach to battling one of the deadliest forms of brain cancer: glioblastoma.

Navigating the blood-brain barrier

Glioblastoma is a particularly aggressive and devastating brain tumor that is notorious for its resistance to conventional treatment methods and its rapid progression.

Despite the best efforts of medical professionals, current treatments – such as surgery, radiation, and chemotherapy – can only extend life expectancy for a limited time, with half of the patients tragically succumbing to the disease within just twelve months of diagnosis.

One of the greatest challenges in treating glioblastoma lies in finding drugs that can effectively cross the blood-brain barrier.

This barrier is a highly selective filtering mechanism that protects the brain from harmful substances, but also prevents many cancer drugs from reaching their target. The blood-brain barrier significantly limits the number of therapeutic options available for brain cancer.

Consequently, neuro-oncologists have been searching for innovative treatments capable of breaching this barrier and directly targeting the tumor, offering hope for improved outcomes in the battle against this deadly disease.

Unexpected role of an antidepressant

Researchers led by Professor Berend Snijder at ETH Zurich, in collaboration with neurologists Michael Weller and Tobias Weiss at the University Hospital Zurich (USZ), have discovered that an antidepressant known as Vortioxetine could play an unexpected role in this battle.

Using a novel screening platform called pharmacoscopy, lead author Sohyon Lee found that Vortioxetine, a widely available and FDA-approved antidepressant, was remarkably effective in targeting glioblastoma cells. “Vortioxetine proved to be the most effective antidepressant,” said Lee.

The pharmacoscopy platform allowed researchers to test hundreds of active substances on living tumor cells from 40 glioblastoma patients, offering unprecedented insight into how drugs interact with cancer cells.

Suppressing cell division in the tumor

Through the meticulous screening of 130 different agents, researchers were surprised to discover that certain antidepressants demonstrated significant effectiveness against brain tumor cells.

These neuroactive drugs, traditionally used to treat mental health conditions, triggered a unique signaling cascade shared by both neurons and cancer cells, effectively suppressing cell division within the tumor.

This unexpected mechanism of action opened new doors in the search for alternative cancer treatments.

Testing a million substances

To further explore these findings, the research team employed advanced computer modeling to test over a million different substances, aiming to deepen their understanding of the interaction between neuroactive drugs and cancer cells.

This extensive modeling revealed crucial insights into why some antidepressants worked so effectively against glioblastoma, while others did not.

The promising laboratory results encouraged the researchers to move their discovery from the lab to animal trials.

When tested on mice with glioblastomas, Vortioxetine – the most effective antidepressant in the screening – produced encouraging results.

Notably, its effectiveness was amplified when combined with standard treatments like chemotherapy and radiation, suggesting its potential as a complementary therapy in glioblastoma treatment protocols.

Antidepressants and brain tumors

The team at ETH Zurich is now preparing for two clinical trials at the University Hospital Zurich, where glioblastoma patients will receive Vortioxetine in addition to standard treatments.

“The advantage of Vortioxetine is that it is safe and very cost-effective,” noted Professor Michael Weller. “As the drug has already been approved, it could soon supplement the standard therapy for this deadly brain tumor.”

However, Weller urges caution, noting that clinical trials are essential before Vortioxetine can be widely prescribed for glioblastoma.

“We don’t yet know whether the drug works in humans and what dose is required to combat the tumor, which is why clinical trials are necessary. Self-medicating would be an incalculable risk,” said Professor Weller.

“So far, it’s only been proven effective in cell cultures and in mice,” said Professor Snijder. Still, he believes this research represents an ideal outcome: “We started with this terrible tumor and found existing drugs that fight against it. We show how and why they work, and soon we’ll be able to test them on patients.”

If successful, this will mark the first time in decades that a new active substance has been found to improve the treatment of glioblastoma, offering newfound hope to patients around the world.

The study is published in the journal Nature Medicine.

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