Title: Scientists Discover Potential Treatment Approach for Glioblastoma Brain Tumors
Subtitle: UC San Francisco researchers find that gabapentin can block neural activity in mice, offering hope for cognitive decline associated with the disease
Published: [Current Date]
UC San Francisco scientists have made a groundbreaking discovery in the field of brain cancer research, revealing that glioblastoma brain tumors can restructure connections in surrounding brain tissue, leading to cognitive deterioration. However, this destructive neural activity can be blocked by the drug gabapentin, according to a study conducted on mice. The findings not only signal a potential treatment approach for glioblastoma but also offer hope for other neural cancers and metastatic brain cancers.
Glioblastoma, a highly challenging brain cancer to treat, is notorious for its ability to cause cognitive decline as it infiltrates neighboring networks in the brain. However, these aggressive alterations may also provide a pathway to its own demise.
A team of researchers at UC San Francisco discovered that these lethal tumors can reshape connections in the surrounding brain tissue through neural activity, resulting in mental decline associated with the disease. Furthermore, the study found that gabapentin, a drug commonly used to prevent seizures, can impede this tumor growth-promoting activity in mice with glioblastoma.
The findings, published in the prestigious scientific journal Nature, represent a hopeful new direction for glioblastoma research, which has historically posed significant challenges for modern cancer treatments.
“Glioblastoma needs a win,” stated neurosurgeon Shawn Hervey-Jumper, MD, who led the study. “This study opens the door to a whole world of treatment possibilities for these patients and a new way of thinking about brain cancer.”
The research was built upon previous studies conducted on mice and brain organoids, clusters of neurons derived from human stem cells grown in laboratory dishes. Hervey-Jumper aimed to understand the implications of the positive-feedback loop observed in brain tumors on human behavior and cognition.
The study included volunteers awaiting glioblastoma surgery, with tumors infiltrating the brain region responsible for speech. To assess the impact of the tumors on cognitive function, the researchers placed tiny electrodes on the speech region’s surface and asked participants to name objects shown to them through pictures. By comparing the results with non-tumor brain regions in the same individuals, the team discovered that tumor-infiltrated areas utilized a broader neural network to identify objects.
This phenomenon is attributed to the degradation of information-processing power within the affected region, akin to the loss of key instruments within an orchestra ensemble affecting the music’s quality.
The study unveils that this interaction between cells is responsible for the cognitive decline observed in brain cancer patients, contrary to previous beliefs that inflammation and tumor growth pressure were the primary causes.
“A brain tumor isn’t just sitting there dying,” Hervey-Jumper explained. “It’s being regulated by the nervous system. It’s having conversations with the cells around it and actively integrating into brain circuits, remodeling the way they behave.”
Recognizing that tumors exploit the brain’s networks, the researchers turned to gabapentin, a medication used to control seizures by reducing excessive electrical activity in the brain. By testing the drug on mice implanted with human glioblastoma cells, the team found that gabapentin effectively prevented tumor expansion.
Krishna, a postdoctoral scholar involved in the study, expressed hope that combining gabapentin with existing glioblastoma therapies could alleviate cognitive decline and potentially extend patients’ lives.
The findings are expected to have implications beyond glioblastoma, potentially aiding in understanding other neural cancers, including spinal tumors, and shedding light on why the brain is often the first site of cancer metastasis.
Hervey-Jumper emphasized that the study encourages oncologists to consider communication networks between cells, such as the positive-feedback loop observed in glioblastoma, as viable targets for treatment in addition to genetic and immunological approaches.
“We haven’t thought about cancer in this way before,” he noted. “The idea that there’s conversation between cancer cells and healthy brain cells is something of a paradigm shift.”
The study received funding from the National Institutes of Health, Robert Wood Johnson Foundation, and the American Brain Tumor Association.
Reference: “Glioblastoma remodeling of human neural circuits decreases survival” by Saritha Krishna, Abrar Choudhury, Michael B. Keough, Kyounghee Seo, Lijun Ni, Sofia Kakaiza, Anthony Lee, Alexander Aabedi, Galina Popova, Benjamin Lipkin, Caroline Cao, Cesar Nava Gonzales, Rasika Sudharshan, Andrew Egladyous, Nyle Almeida, Yalan Zhang, Annette M. Molinaro, Humsa S. Venkatesh, Andy GS Daniel, Kiarash Shamardani, Jeanette Hyer, Edward F. Chang, Anne Findlay, Joanna J. Phillips, Srikantan Nagarajan, David R. Raleigh, David Brang, Michelle Monk, and Shawn L. Hervey-Jumper, May 3, 2023, Nature. DOI: 10.1038/s41586-023-06036-1