When treating brain tumors, many cancer drugs fail at the blood-brain barrier - the active substances do not reach the tumor in the first place. In a study conducted by ETH Zurich and the University Hospital Zurich, a well-known antidepressant that overcomes this barrier and effectively combats cancer cells has now proved to be a promising solution.
Glioblastoma is an aggressive brain tumor that is currently incurable. Those affected can be given more time to live with surgery, chemotherapy and radiotherapy, but half of patients die within twelve months of diagnosis.
The drug treatment of proliferating brain tumors faces particular problems: Many cancer drugs fail in brain tumors because the blood-brain barrier prevents the drugs from reaching the brain. Researchers led by ETH Professor Berend Snijder have now found an active substance that effectively combats glioblastomas, at least in the laboratory. These are the antidepressant vortioxetine and related substances. The drug is known to be able to cross the blood-brain barrier, and the antidepressant is also approved by Swissmedic, among others, and is inexpensive.
Snjider’s postdoc Sohyon Lee found it together with Tobias Weiss, senior physician at the Department of Neurology at the USZ, using pharmacoscopy, a special screening platform that the researchers have developed over the past ten years at ETH Zurich.
Hundreds of substances are tested simultaneously
With pharmacoscopy, ETH researchers can simultaneously test hundreds of active substances on living cells from human cancer tissue. In their study, they focused primarily on neuroactive substances that cross the blood-brain barrier, such as antidepressants, antiparkinsonian drugs or antipsychotics. In total, they tested more than 130 different agents on tumor tissue from 40 patients who had recently undergone surgery at the University Hospital of Zurich or the Cantonal Hospital of St. Gallen and made their tissue available for research. The ETH researchers also used a computer model to test over a million substances for their effectiveness against glioblastomas.
Antidepressants surprisingly effective
The tests showed that some of the antidepressants tested were surprisingly effective against the tumor cells. Vortioxetine proved to be the most effective antidepressant. The drug also showed good efficacy in subsequent trials on mice with glioblastoma, especially in combination with the current standard treatment. In a next step, a group of ETH and USZ researchers is now preparing clinical studies on the use of vortioxetine for the treatment of glioblastomas.
Drug is already approved and cost-effective
“The advantage of vortioxetine is that it has already been approved and is very cost-effective,” says Michael Weller, Director of the Department of Neurology at the University Hospital Zurich and co-author of the study. “It could therefore supplement the standard therapy for this fatal brain tumor after the studies that are still required.”
No self-medication with vortioxetine
However, its effectiveness has only been proven in the laboratory and in mice. Michael Weller therefore warns patients not to take vortioxetine without medical supervision. “We don’t yet know whether the drug works in humans and what dose is required to combat the tumor. That’s why clinical trials are necessary.” However, if vortioxetine proves to be effective, this will be the first time in decades that an active substance has been found that takes the treatment of glioblastoma a major step forward.
Literature reference
Lee S, Weiss T, Bühler M, et al. High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity. Nature Medicine (2024), doi: 10.1038/s41591-024-03224-y
