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Glioblastoma’s hidden weakness may have been found

Glioblastoma, a particularly aggressive brain cancer, stealthily infiltrates the brain, often leading to significant cognitive decline in those it afflicts. Paradoxically, this very insidious characteristic might also hold the key to its downfall.

A team of researchers at UC San Francisco have made the startling discovery that neural activity within these lethal tumors can modify connections in adjacent brain tissue, instigating the cognitive deterioration associated with the disease. Their study, published in the prestigious journal Nature, also revealed that the drug gabapentin, typically prescribed for seizure prevention, successfully halted this growth-stimulating activity in mice with glioblastoma.

These findings offer a glimmer of hope in the fight against a disease that continues to resist even the most advanced cancer treatments.

Medicine is in desperate need of a breakthrough when it comes to glioblastoma, believes Shawn Hervey-Jumper, MD, a neurosurgeon who spearheaded the study, along with postdoctoral scholar Saritha Krishna, PhD. This research opens up a whole new realm of treatment possibilities for these patients and introduces a fresh perspective on brain cancer, Hervey-Jumper said.

At the inception of Hervey-Jumper’s study, scientists had recently uncovered that brain tumors are fueled by a self-perpetuating cycle. This cycle begins when cancer cells produce substances functioning as neurotransmitters. The surplus of neurotransmitters triggers hyperactivity in neurons, which, in turn, promotes the growth of the cancer cells.

Drawing on previous studies conducted on mice and brain organoids (small clusters of neurons derived from human stem cells grown in laboratory conditions), Hervey-Jumper decided to explore the implications of this feedback loop on human cognition and behavior in the context of brain cancer.

The researchers enlisted volunteers diagnosed with glioblastoma, whose tumors had invaded the brain region governing speech. In the moments before surgical intervention, Hervey-Jumper applied a grid of minuscule electrodes to the speech area, asked the volunteers to name objects shown in pictures, and compared the results with those from unaffected brain regions in the same participants. It was found that the patients’ tumor-affected brain regions engaged a more extensive neural network to identify the objects they were viewing.

Hervey-Jumper likens this phenomenon to the disruption of an orchestra’s synchrony, resulting in diminished performance. He explained, “When you lose the cellos and the woodwinds, the remaining musicians can’t deliver the piece as effectively.” The brain cells entangled in the tumor are so compromised that additional cells from further afield are recruited to carry out tasks previously managed by a smaller area.

The research suggests that it’s this intercellular interaction that triggers the cognitive decline associated with brain cancer, rather than inflammation and pressure from tumor growth, as previously hypothesized.

Hervey-Jumper elaborated that a brain tumor isn’t merely a dying mass. It’s being regulated by the nervous system, engaging in dialogue with the surrounding cells and actively integrating into brain circuits, altering their behavior.

Upon recognizing that the tumors were exploiting the brain’s networks, the researchers tested gabapentin, a drug known to control seizures by reducing excess electrical activity in the brain, on mice implanted with human glioblastoma cells. The results were promising.

Gabapentin effectively halted the tumor’s expansion, Krishna reported. This gives hope that combining gabapentin with other glioblastoma therapies could help mitigate some of the cognitive decline observed in patients and potentially prolong their lives.

The team anticipates that these findings could apply to other neural cancers, such as spinal cancers, and might shed light on why the brain is often the primary site of metastasis in many types of cancer.

Hervey-Jumper encourages cancer specialists to consider the possibility of targeting communication networks between cells, like the positive-feedback loop in glioblastoma, in addition to employing genetic and immunological approaches.

We need to reshape our understanding of cancer, he urged. The notion that there’s a dialogue happening between cancer cells and healthy brain cells represents a significant shift in our thinking, he said.

This study not only presents a novel perspective on brain cancer but also provides an alternative approach to tackling this formidable disease. The concept that cancerous cells are not merely multiplying but are actively communicating and altering their surrounding environment is an enlightening paradigm shift that may be the key to more effective treatments.

With the drug gabapentin showing promise in halting the growth of these aggressive tumors, there’s a glimmer of hope that this new line of research could lead to significant strides in the battle against glioblastoma and other forms of brain cancer.

This study, however, is just the beginning, and more research is needed to fully understand these interactions and how best to target them for treatment. Yet, the notion that the communication between healthy and cancerous cells could be manipulated to halt or slow the growth of tumors is an exciting development in the field.




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