Researchers have utilized a drug screening platform they created to demonstrate that an antidepressant currently available on the market can kill glioblastoma tumor cells in a laboratory setting.
Glioblastoma is an extremely aggressive brain cancer that is currently considered untreatable. While oncologists can extend a patient’s life through surgeries, radiation therapy, and chemotherapy, tragically, half of those diagnosed succumb to the disease within a year.
Finding effective medications for brain tumors is challenging because many cancer treatments cannot penetrate the blood-brain barrier, thus limiting treatment options. As a result, neuro-oncologists have been diligently searching for drugs that can reach brain tumors and eliminate them.
Led by ETH Zurich’s Professor Berend Snijder, researchers have uncovered a compound that shows promise against glioblastomas in vitro: the antidepressant known as vortioxetine. This drug is relatively inexpensive and has been approved by regulatory bodies like the FDA in the United States and Swissmedic, enabling it to cross the blood-brain barrier effectively.
Sohyon Lee, a postdoc and the primary author of the research, discovered this medication using pharmacoscopy, a unique screening method developed at ETH Zurich over several years. The findings of this study were recently published in the journal Nature Medicine. In this research, ETH Zurich’s team collaborated with various hospitals, particularly under the guidance of neurologists Michael Weller and Tobias Weiss at the University Hospital Zurich (USZ).
Simultaneously testing hundreds of substances
With the pharmacoscopy method, the researchers at ETH Zurich can evaluate hundreds of active compounds simultaneously on living cells derived from human cancer tissues. Their research primarily investigated neuroactive compounds capable of crossing the blood-brain barrier, including antidepressants, Parkinson’s medications, and antipsychotics. The study analyzed up to 130 different substances on tumor tissues obtained from 40 patients.
To identify which substances impacted cancer cells, the researchers employed imaging techniques alongside computer analysis. Previously, Snijder’s team had utilized the pharmacoscopy platform exclusively for studying blood cancers, from which they derived treatment alternatives. Now, glioblastomas are the first solid tumors they have systematically examined in hopes of repurposing existing drugs.
For the study, Lee analyzed fresh cancer tissue from patients who had recently undergone surgery at the University Hospital Zurich. The researchers then processed this tissue in their lab and screened it using the pharmacoscopy platform. Results indicating which drugs were effective against the cancer cells were obtained just two days later.
Surprisingly effective antidepressants
The outcomes revealed that some, but not all, of the antidepressants tested exhibited unexpected efficacy against tumor cells. These drugs were particularly effective when they rapidly initiated a signaling cascade important for neuronal progenitor cells, which also inhibits cell division. Among them, vortioxetine was identified as the most effective antidepressant.
The researchers also employed a computer model to evaluate over a million substances for their effectiveness against glioblastomas. They discovered that the joint signaling mechanism between neurons and cancer cells is crucial in determining why some neuroactive drugs are effective while others are not.
In a final phase, researchers from the University Hospital Zurich assessed vortioxetine’s effects on mice with glioblastoma, finding that the drug performed well, especially when combined with the standard treatment regimen.
The ETH Zurich and USZ research team is now gearing up for two clinical trials. One will involve treating glioblastoma patients with vortioxetine along with standard treatments (surgery, chemotherapy, radiation). The second trial will involve a personalized selection of drugs for patients, determined individually using the pharmacoscopy method.
Widely available and cost-effective drug
“The great thing about vortioxetine is that it’s safe and very affordable,” explains Michael Weller, a Professor at University Hospital Zurich, who is also the Director of the Neurology Department and a co-author of the study published in Nature Medicine. “Since the drug is already approved, there won’t be a long approval process, allowing it to complement the standard therapy for this severe brain tumor in the near future.” He is hopeful that oncologists will be able to utilize it swiftly.
However, he cautions patients and their families against self-medicating with vortioxetine without proper medical guidance. “We currently lack information on the drug’s efficacy in humans and the required dosage for tumor treatment, which is why clinical trials are essential. Self-medication could pose a significant risk.”
Snijder also urges caution regarding the use of the antidepressant for glioblastomas: “So far, its efficacy has only been demonstrated in cell cultures and mice.”
Nonetheless, he believes the study has achieved an optimal result: “We started with this challenging tumor and identified existing medications that combat it. We elucidate how and why they work, and soon, we’ll be able to test them in patients.” If vortioxetine proves effective, it would mark the first time in many years that a medication has been discovered to enhance glioblastoma treatment.
