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Glioblastoma is an extremely aggressive brain tumor that is currently incurable. Cancer doctors can increase the life expectancy of their patients with surgery, radiation, chemotherapy or surgical procedures. Still, half of patients die within a year of diagnosis. Finding effective drugs against brain tumors is challenging because many cancer drugs are unable to cross the blood-brain barrier and enter the brain. This reduces the number of available treatments. So neuro-oncologists have been working hard for the past few years to identify better drugs that can reach the brain and eliminate the tumor.
Researchers led by Professor Bernd Schneider of ETH Zurich have discovered a chemical that successfully fights glioblastoma, at least in vitro: vortioxetine, an antidepressant drug. Scientists know that this inexpensive drug, which is already available, works.
Pharmacoscopy: A game-changing tool for cancer treatment
Snyder’s postdoc and lead author of the study, Sohyeon Lee, found this by using pharmacoscopy, a special screening platform that researchers have developed at ETH Zurich over the past years. The study findings were recently published in the journal Nature Medicine. In this study, the researchers at ETH Zurich worked together with colleagues from various hospitals, in particular with the group of neurologists Michael Weller and Tobias Weiss at the University Hospital Zurich (USZ).
With the help of pharmacoscopy, researchers at ETH Zurich can test hundreds of active substances simultaneously on living cells from human cancer tissue. Their study focused mainly on neuroactive substances that cross the blood-brain barrier, such as antidepressants, Parkinson’s medication and antipsychotics. In total, the research team tested 130 different agents on tumor tissue from 40 patients.
To determine which substances have an effect on the cancer cells, the researchers used imaging techniques and computer analysis. Previously, Snyder and his team used the pharmacoscopy platform only to analyse blood cancers (see ETH News) and derive treatment options from this. Glioblastomas are the first solid tumours that they have systematically investigated using this method in order to use existing drugs for new purposes.
For the screening, Lee analyzed fresh cancer tissue from patients who had recently undergone surgery at the University Hospital Zurich. Researchers at ETH Zurich then processed this tissue in the laboratory and screened it on a pharmacoscopy platform. Two days later, the researchers received results showing which agents worked on cancer cells and which did not.
Glioblastoma: A deadly and incurable brain tumor
The results made it clear that some, but not all, of the antidepressant drugs tested were unexpectedly effective against tumor cells. These drugs proved particularly effective when they immediately activated a signaling cascade that is important for neuronal progenitor cells but also suppresses cell division. Vortioxetine proved to be the most effective antidepressant.
The ETH Zurich researchers also used a computer model to test more than one million substances for their effectiveness against glioblastoma. They found that the combined signaling cascade of neurons and cancer cells plays a decisive role and explains why some neuroactive drugs work while others do not. In a final step, researchers at the University Hospital Zurich tested vortioxetine on mice with glioblastoma. The drug showed good efficacy in these tests as well, especially in combination with existing standard treatments.
The group of ETH Zurich and USZ researchers is now preparing two clinical trials. In one, glioblastoma patients will be treated with vortioxetine in addition to standard treatments (surgery, chemotherapy, radiation). In the other, patients will receive a personalized drug selection, which the researchers will determine for each individual using a pharmacoscopy platform.
“The advantage of vortioxetine is that it is safe and very affordable,” says Michael Weller, professor at the University Hospital Zurich, director of the Department of Neurology and co-author of the study published in Nature Medicine. “Since the drug has already been approved, it does not have to go through a complicated approval process and could soon complement the standard treatment for this deadly brain tumor.” He hopes that oncologists will soon be able to use it.
However, he warns patients and their relatives against obtaining vortioxetine on their own and taking it without medical supervision. “We do not yet know whether this drug works in humans and what dose is needed to fight the tumor, which is why clinical trials are necessary. Prescribing the drug on your own would be an unthinkable risk.” Snyder also warns against rushing to use the antidepressant on glioblastoma: “So far, it has only been proven effective in cell cultures and mice.”
Nevertheless, he believes this study has achieved an ideal result: “We started from this terrible tumor and found existing drugs that fight against it. We show how and why they work, and soon we will be able to test them on patients.” If vortioxetine proves effective, it will be the first time in recent decades that an active substance has been found to improve the treatment of glioblastoma.
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