FDA-approved antidepressant treats incurable brain cancer in preclinical trial: ScienceAlert

A widely available and inexpensive antidepressant could soon save lives from a very different kind of disease.

The growth of the most aggressive and deadly brain tumor, glioblastoma, was effectively suppressed in both cases ex vivo human tissue samples and in living mice an FDA-approved serotonin modulator currently used to treat severe depression.

It is not a cure, but it can provide some relief and be an effective part of the treatment of glioblastoma patients. Human clinical trials are the next step; Patients are warned against self-medication at this stage.

“The advantage of vortioxetine is that it is safe and very cost-effective,” says neurologist Michael Weller of the University Hospital of Zurich in Switzerland. “Since the drug is already approved, it does not have to go through a complex approval process and could soon complement the standard therapy for this deadly brain tumor.”

Glioblastomas are rare, but when they occur, they are difficult to beat. The tumor typically occurs in the brain or brainstem and grows quickly and aggressively. There is currently no cure, meaning it is usually fatal 95 percent of patients within five years. Treatment usually includes radiation therapy and chemotherapy sometimes an operation to try to remove as much tumor as possible.

A noninvasive treatment that can complement existing interventions to improve outcomes is something doctors would like to have, but since few cancer drugs can cross the blood-brain barrier, the options are limited.

A research team led by molecular biologist Sohyon Lee from ETH Zurich used cultured human tissue grown from samples donated by glioblastoma patients undergoing surgical treatment to see whether existing drugs could effectively suppress the growth of cancer cells. They focused primarily on antidepressants, antipsychotics, and drugs used to treat Parkinson's disease.

In total, they tested 132 drugs on cultured tissue from 27 glioblastoma patients and cataloged more than 2,500 drug reactions. And they surprisingly found that some antidepressants were effective in suppressing the development of cancer cells, including serotoninA modulator called vortioxetine.

One of the effects of vortioxetine is Activate signal cascadesa series of reactions in a cell triggered by a stimulus. These cascades suppress cell division, which is how cancer grows and spreads.

Computer simulations showed that the simultaneous cascade of nerve cells and cancer cells was necessary to inhibit the cancer, which is why only some of the antidepressants were effective – they don't all work in the same way.

The next step was to test the drugs in a living, breathing system: mice with glioblastoma. Mice were transplanted with glioblastoma tumors and then assigned to a group. The control group remained untreated, while a second group of mice was treated with the SSRI antidepressant citalopram. Finally, a third group was treated with vortioxetine.

Comparisons 38 days after tumor implantation showed that the vortioxetine treatment group had significantly less tumor growth and invasiveness than the control and citalopram groups, which showed similar results.

In a follow-up experiment, another sample of glioblastoma mice was treated with standard chemotherapy drugs. Another group was given vortioxetine, while a third group was not given vortioxetineI have not received any other treatment.

Similarly, the vortioxetine group had a 20 to 30 percent higher survival rate than the chemotherapy-only group, not only in the short term but also in the long term.

Given these promising preclinical results, further studies in live human patients could shed light on whether we may already have a ready-to-use glioblastoma therapy.

“We do not yet know whether the drug works in humans and what dose is required to combat the tumor, which is why clinical studies are necessary,” Weller warns. “Self-medication would be an incalculable risk.”

Still, the drug shows more promise than ever for treating this devastating cancer, giving some hope to the estimated 250,000 people diagnosed with glioblastoma each year.

“We started with this terrible tumor and found existing drugs to fight it,” says molecular biologist Berend Snijder the ETH Zurich. “We are showing how and why they work, and we will soon be able to test them on patients.”

The research was published in Natural medicine.