Scientists discover hidden weakness in deadly brain cancer

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Scientists discover hidden weakness in deadly brain cancer

Scientists discover hidden weakness in deadly brain cancer.

Glioblastoma, a notoriously difficult-to-treat brain cancer, causes cognitive decline by infiltrating adjacent networks in the brain. However, this aggressive attack can also become its mortal wound.

A UCSF research team has discovered that these deadly tumors alter the connectivity of surrounding brain tissue through neural activity.

This structural adjustment contributes to the mental decline associated with the disease.

Additionally, they found that gabapentin, a prescription drug commonly used to prevent seizures, blocked this tumor growth-promoting activity in mice with glioblastoma.

Scientists discover hidden weakness in deadly brain cancer

The findings, published in the journal Nature, offer a promising new direction for studying a disease that is beyond the reach of even the most advanced and sophisticated anticancer drugs.

“Glioblastoma needs a win,” said neurosurgeon Shawn Hervey-Jumper, MD, who along with postdoctoral scholar Saritha Krishna Ph.D. co-led the research. “This study opens a door to therapeutic possibilities for these patients and provides a new way of thinking about brain cancer research.”

When Hervey-Jupper began her research, scientists had recently discovered that brain tumors are fueled by a positive feedback loop.

It starts when cancer cells produce substances that act as neurotransmitters. This “extra” supply of neurotransmitters stimulates neurons to become hyperactive, which in turn stimulates the growth of cancer cells.

Building on previous work in mice and brain organoids (small bundles of neurons derived from human stem cells grown in a dish), Hervey-Jupper focused on how brain cancer feedback loops affect humans Behavioral and cognitive effects.

The team recruited volunteers awaiting surgery for glioblastoma whose tumors had infiltrated the brain region that controls language.

Just before surgery on the tumor, Hervey-Jupper placed a grid of tiny electrodes on the surface of the speech area, showed pictures to the volunteers, and asked them to say what they saw.

The team then compared the results to normal-looking, non-tumor regions of the brains of the same participants. They found that the participants’ tumor-infiltrated brain regions used a wider network of brain regions to recognize what they were seeing.

Scientists discover hidden weakness in deadly brain cancer

Cancer is a dialogue between cells

Hervey-Jupper attributes this to a degeneration of information processing in this area of the brain. He likens it to a symphony orchestra, where the musicians play in sync to create a beautiful movement.

“If you lose the cello and the woodwinds, the remaining players can’t play music as well as they used to,” he said. “The brain cells tethered to the tumor are severely damaged and have to recruit other brain cells from further afield. Complete missions that would otherwise be controlled by smaller areas.”

The study suggests that it is this interplay between cells that is responsible for the cognitive decline associated with brain cancer, rather than the stress of inflammation and tumor growth that scientists believe.

“A brain tumor isn’t just sitting there waiting to die. It’s being regulated by the nervous system. It’s talking to the cells around it and actively engaging with brain circuits, reshaping the way they behave,” Hervey-Jumper said.

Never Thought About Cancer This Way

Now, researchers know that tumors are exploiting brain networks. So they turned to gabapentin, a drug that controls seizures by dampening excess electrical activity in the brain, and tested them in mice inoculated with human glioblastoma cells.

“Gabapentin actually stopped the tumor from expanding,” Krishna said. “This gives us hope that combining gabapentin with other glioblastoma therapies could prevent some of the cognitive decline we’re seeing in patients and perhaps extend their lives.”

These findings are likely to translate to other neurological cancers, such as those of the spine, and may help explain why the brain is the first site of metastasis for many cancers.

Hervey-Jumper said the study encourages cancer experts to consider communication networks between cells, like the positive feedback loops in glioblastoma, as potential therapeutic targets alongside genetic and immunological approaches. “We’ve never thought about cancer in this way before,” he said. “The idea that there is a dialogue between cancer cells and healthy brain cells is a paradigm shift.”