Chilling brain tumor cells to stop dividing without killing healthy cells dramatically prolonged survival in an animal model of glioblastoma (GBM).Findings published in scientific progressmay lead to new treatments for this aggressive and deadly cancer for which there is no effective treatment.
“Unfortunately, glioblastoma patients don’t have many options today. These brain tumors almost always recur,” said study leader Syed Faaiz Enam, PhD, UTSW adult neurology resident. . I am studying biomedical engineering at Duke University. “By lowering body temperature, it shows that we may be able to accomplish things that standard treatments cannot.”
More than 300,000 cases of glioblastoma are diagnosed worldwide each year, making it the most common primary malignant brain tumor in adults. Despite decades of research, glioblastoma patients live an average of 15-18 months after diagnosis, with only a 7% survival rate after 5 years.
Most patients usually have surgery to remove the primary tumor, followed by chemotherapy and radiation therapy to kill any remaining malignant cells, but these cancers are usually within 1 to 2 cm of the original tumor. Dr. Enam said it will recur in .
While at Duke, Dr. Enam envisioned a new way to treat brain tumors using hypothermia while working in the lab of Dr. Ravi Bellamkonda, then Dean of the Pratt School of Engineering at Duke and now President of Emory University. .
To test this idea, Dr. Enam and colleagues exposed human and rat glioblastoma cell lines to cold temperatures for varying lengths of time. They found that temperatures of 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) for just 18 hours a day can prevent these cells from dividing, slowing their metabolism and promoting cancer growth. It was found that the production of signaling molecules known to be decreased. Additionally, trials have shown that treatments such as chemotherapy and immunotherapy act synergistically with cold temperatures to kill more cultured cells.
To assess the feasibility of the cooling strategy in live animals, Dr. Enam worked with mechanics at Duke to create a cooling device that could be applied to the brains of rats with glioblastoma tumors of human or rat origin. transplanted. Even if the tumors were not sufficiently cooled, rats that received cooling survived more than twice as long as rats that did not switch on the device, jumping from 3.9 weeks to 9.7 weeks. Animals that received survived the entire study period.
Dr. Enam says this “cytostatic” or growth-arresting hypothermia will eventually be used to buy patients time while conventional treatments are tested or new treatments are discovered. stated that it could be Instead of modern, targeted approaches, he said, the approach would manipulate fundamental physics to broadly impact biology. He therefore hopes that the results seen in rats will be translated to humans. patented the first iteration of the device of
Dr. Enam was awarded a Sprouts grant under mentorship from UTSW’s Peter O’Donnell Jr. Brain Institute to further develop his research. He continues this research at his UTSW, said his Sprout mentor Amyn Habib, M.D., Ph.D., professor of neurology at the O’Donnell Brain Institute and Harold C. Simmons Comprehensive Cancer Center. said he shared the research space of his lab with Dr. Enam. Dr. Enam is currently prototyping the device, testing it in pigs, and continuing clinical research as a neurologist.
“This is an interesting approach to prevent glioblastoma growth that is different from chemotherapy approaches,” said Dr. Habib. “Dr. Enam’s research adds another dimension to a broader effort to develop treatments for brain tumors.”
Dr. Habib explained that many of these efforts at UTSW are focused on identifying and finding ways to block the molecular pathways that cause glioblastoma to spread to surrounding brain tissue. . The research studies use genomic, metabolomics, and biophysical approaches as well as drug discovery, and include a clinical trial started this year based on the finding that existing drugs inhibited tumor growth in animal models. I’m here.
UT Southwestern also has one of the largest national repositories of clinically annotated patient-derived xenograft mouse models of high-grade glioma and brain metastases. This important asset plays an important role in helping scientists better understand how brain tumors spread and identify potential treatments.
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