Glioblastoma is a highly aggressive brain tumor, with no cure currently available. While treatments like surgery, radiation, and chemotherapy can extend life expectancy, the prognosis remains grim. Half of the patients die within a year of diagnosis. One of the key challenges in treating glioblastoma is the blood-brain barrier, which limits the efficacy of many cancer drugs by preventing them from reaching the brain.
In a breakthrough study led by ETH Zurich’s Professor Berend Snijder, researchers have identified an antidepressant called vortioxetine as a potential treatment for glioblastomas in lab settings. Vortioxetine, already approved by regulatory agencies such as the FDA and Swissmedic for treating depression, is capable of crossing the blood-brain barrier, making it a promising candidate for treating brain tumors.
The discovery was made through a novel screening platform known as pharmacoscopy, developed at ETH Zurich. Using this platform, Snijder’s team, including lead author Sohyon Lee, was able to test hundreds of drugs simultaneously on living cancer cells. The study was conducted in collaboration with neurologists Michael Weller and Tobias Weiss from the University Hospital Zurich (USZ).
Testing Hundreds of Substances on Tumor Cells
The researchers tested around 130 different substances, focusing primarily on neuroactive drugs that can cross the blood-brain barrier, such as antidepressants, Parkinson’s medications, and antipsychotics. The team used tissue samples from 40 glioblastoma patients who had recently undergone surgery, allowing for real-time analysis of drug efficacy.
The screening revealed that certain antidepressants, including vortioxetine, were unexpectedly effective in suppressing tumor cell growth. Vortioxetine stood out as the most effective, initiating a signaling cascade that not only affects neuronal cells but also inhibits cancer cell division.
Promising Results in Animal Trials
Following promising results in cell cultures, the researchers tested vortioxetine on mice with glioblastomas. In combination with existing standard treatments such as surgery, chemotherapy, and radiation, vortioxetine showed significant efficacy in slowing tumor growth.
The team is now preparing two clinical trials. In one, glioblastoma patients will receive vortioxetine alongside standard treatments. In the other, patients will receive personalized drug therapies, determined by the pharmacoscopy platform.
An Inexpensive and Safe Drug
One of the key advantages of vortioxetine is its safety profile and low cost, making it an attractive candidate for future treatments. Since it is already approved for use, the process to integrate it into glioblastoma treatment protocols could be expedited. However, Professor Weller cautions that further clinical trials are essential before the drug can be recommended for general use. He advises patients not to self-medicate, as the correct dosage and efficacy in humans are yet to be determined.
While the findings are currently limited to lab and animal studies, the research marks a significant step forward. If clinical trials are successful, vortioxetine could become the first new drug in decades to improve glioblastoma treatment outcomes.
Reference:
1. Lee, Sohyon, Tobias Weiss, Marcel Bühler, Julien Mena, Zuzanna Lottenbach, Rebekka Wegmann, Miaomiao Sun, et al. “High-Throughput Identification of Repurposable Neuroactive Drugs with Potent Anti-Glioblastoma Activity.” Nature News, September 20, 2024. https://www.nature.com/articles/s41591-024-03224-y.
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