Can Prozac Fight Brain Cancer?

A Stanford study on brain tumors suggests that the common antidepressant Prozac might be able to treat brain cancer. If confirmed, these findings would be a huge success in United States cancer research.

The common antidepressant Prozac may be able to treat brain cancer, according to a study on glioblastoma at Stanford University.

Professor of Pathology at Stanford, Paul Mischel, MD and postdoctoral scholar Junfeng Bi, PhD, published a promising discovery in the respected science journal Cell Report that found that the common antidepressant fluoxetine (commonly known as Prozac) targets the brain tumor glioblastoma in laboratory mice.

The researchers also found data from electronic medical records that showed that people with glioblastoma who were given Prozac in addition to their standard treatment for the disease lived longer.

Mischel explained glioblastoma to Stanford Medicine: "Glioblastoma is a terrible cancer. It's the most common malignant brain cancer in adults, but we don't have any way to detect it early, and treatments are often ineffective."

Glioblastomas tumors are very unique. Unlike many brain tumors, these tumors are located behind a thing called “blood-brain barriers.”

Blood-brain barriers are a network of blood vessels and tissue that is made up of closely spaced cells. They help keep harmful substances from reaching the brain. Due to their location, the blood-brain barriers make glioblastoma tumors especially difficult to treat.

Another complicated fact about glioblastoma is that they are known to have many copies of cancer-associated genes. One of these cancer-associated genes is called the epidermal growth factor receptor, or EGFR.

Dr. Mischel began studying glioblastoma, an often deadly cancer, many years ago. However, he explained that because glioblastoma tumors are so complicated, he was still very surprised to find their link to Prosac.

"In most cancers, EGFR is mutated to become more active, but in glioblastomas, the EGFR gene is instead amplified many times. But previous work in my lab showed that targeting these amplifications directly wasn't successful," said Dr. Mischel.

The start of the Stanford researchers' discovery came with a few findings.

  • In glioblastoma cells, the balance between cholesterol and lipids, a type of fat, is often very off-balance.
  • Lipids found in glioblastoma cells are very important in EGFR signaling (one of the most important pathways that regulate cell growth and survival).
  • A specific type of lipid called sphingolipid is especially important in EGFR signaling.

People with glioblastomas who had high levels of an enzyme related to sphingolipids (SMPD1) had significantly shorter lifespans than patients with lower levels of the enzyme.

The goal then became finding something that could block enzymes linked to SMPD1 and also cross the blood-brain barrier, which turned out to be the drug Prozac.

"We nearly fell off our chairs when we saw that fluoxetine, or Prozac, achieves both of these goals," Dr. Mischel said, "It's known to be safe, it can enter the brain, and it can inhibit SMPD1. And when we gave Prozac at a safe dose to mice with human glioblastomas, the levels of the EGFR oncogene went down significantly, and the tumors melted away and didn't come back. It's something we've never seen before."

Prozac is one of the most commonly used antidepressants in the United States. It is also one of the few medicines approved by the FDA for kids and teenagers. Since Prozac is very popular, the researchers decided to search for proof of its effects on glioblastoma among current users.

They were able to find a small sample size of people with glioblastomas who had also been taking Prozac during their illnesses. This was done by surveying the electronic medical records of large insurance claim databases.

The medical records were able to confirm their lab research.

"We found that patients who had received Prozac, along with the standard of care for glioblastomas, lived much longer than the control group," Mischel said.

While the Stanford researcher’s findings are quite promising, more research needs to be done to solidify the benefits of Prozac in fighting brain cancer.

Together with the National Brain Tumor Society, the researchers plan to begin a clinical trial to see how Prozac affects people with glioblastomas.

"We feel this is poised to be tested in patients quite soon," said Dr. Mischel.


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