Scientists discover hidden vulnerability to deadly brain cancer – ScienceDaily


Hard-to-treat, glioblastoma robs a person of a person’s mental faculties as it spreads, yet the malignant tumor’s ability to infiltrate neighboring networks in the brain can also prove undoing.

Scientists at the University of California, San Francisco, have discovered that neural activity in these killer tumors can rebuild connections in surrounding brain tissue, causing the cognitive decline associated with the disease, and that the drug gabapentin, commonly used to prevent seizures, can block this growth-inducing activity. . in mice with glioblastoma.

The results, which appear in natureprovides a hopeful new direction for research into a disease that defies even the most advanced types of cancer drugs.

“Glioblastoma needs to win,” said neurosurgeon Sean Hervey Jumper, who led the study along with postdoctoral researcher Saritha Krishna, PhD. “This study opens the door to a whole world of treatment possibilities for these patients and a new way of thinking about brain cancer.”

When Hervé Gamper began his studies, scientists had recently discovered that brain tumors are fueled by a positive feedback loop. It begins when cancer cells produce substances that can act as neurotransmitters. This “extra” supply of neurotransmitters stimulates neurons to become overactive, which in turn stimulates the growth of cancerous cells.

Building on previous studies in mice and brain organoids (small bundles of neurons derived from human stem cells grown in petri dishes), Hervé Jumper focused on what the feedback loop means for human behavior and cognition in brain cancer.

The team recruited volunteers awaiting surgery for glioblastoma whose tumors had infiltrated the area of ​​the brain that controls speech. Just before operating on the tumor, Hervé Gamper placed a grid of tiny electrodes on the surface of the speech area, showed the volunteers pictures and asked them to name what they saw.

The research team then compared the results to normal, non-tumor regions of the brain from the same participants. They found that the tumor-infiltrated brain regions used a neural network wider than the brain region to try to determine what they were seeing.

Cancer as a conversation between cells

Hervey-Jumper attributes this to the deterioration of information-processing power in that region of the brain. He likens it to an orchestra where the musicians play in sync making the music work.

“If you lose the cello and the woodwinds,” he said, “the remaining players will not be able to carry the piece the way they can.” Brain cells associated with the tumor are so damaged that others must be recruited from far away to perform tasks that were once controlled by a smaller area.

The study showed that it is this interaction between cells that causes the cognitive decline associated with brain cancer, and not the inflammation and stress from tumor growth, as the scientists had thought.

“Brain tumors are not just about death,” said Hervé Gamper. “It’s regulated by the nervous system. It’s having conversations with the cells around it and actively integrating into brain circuits, reshaping the way you act.”

We didn’t think of cancer that way

Now, researchers knew that tumors were tapping into brain networks. So, they turned to gabapentin, which controls seizures by reducing excess electrical activity in the brain, and tested it on mice grafted with human glioblastoma cells.

“Gabapentin has been very successful in preventing the tumor from expanding,” Krishna said. “This makes us hopeful that combining gabapentin with other treatments for glioblastoma could prevent some of the cognitive decline we see in patients and possibly extend their lives.”

The findings have the potential to translate to other neuroblastomas, such as those of the spine, and may help explain why the brain is the primary site of metastasis in many cancers.

Hervé Gamper said the study encourages cancer specialists to consider communication networks between cells, such as the positive feedback loop in glioblastoma, as potential targets for treatment, along with genetic and immunological approaches.

“We haven’t thought about cancer in this way before,” he said. “The idea that there is a conversation between cancer cells and healthy brain cells is kind of a paradigm shift.”

Funding: This study was supported by the National Institutes of Health (grants K08NS110919, P50CA097257, F30CA246808, T32GM007618, K99CA25200, R01NS100440, R00DC013828, R01NS092597, DP1NS111132, and K08CA212279 (Foundation Robert Wood Johnson) and US Grant 7425 MSSF1900021).


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