Scientists at the University of Virginia Comprehensive Cancer Center have developed an experimental strategy for treating glioblastoma, the most common and aggressive malignant brain tumor in adults. The new approach aims to overcome significant obstacles that have historically limited the effectiveness of existing therapies for this deadly disease.
The research team, led by Roger Abounader, MD, PhD, identified tiny genetic molecules known as microRNAs that can interfere with several genes responsible for the development and growth of glioblastoma. To deliver these molecules into the brain, the researchers combined specialized nanoparticles, focused ultrasound, and microscopic bubbles. Together, these technologies offer a way to temporarily cross the brain’s protective barrier, which normally prevents many treatments from reaching brain tumors and other neurological conditions.
Bypassing the Blood-Brain Barrier
Glioblastoma is exceptionally difficult to manage because cancer cells spread into surrounding healthy brain tissue, making it nearly impossible for surgeons to remove the entire tumor. Another major challenge is the brain’s natural blood-brain barrier. This protective system shields the brain from harmful substances, including toxins and infectious agents, but it also blocks many drugs that could otherwise be used to attack brain cancer.
Current treatment generally begins with surgery to remove as much of the tumor as possible. Patients then receive radiation therapy and chemotherapy to help control the remaining cancer and extend survival. Despite these efforts, glioblastoma remains a leading cause of cancer-related death, claiming more than 13,000 lives in the United States each year.
The UVA researchers are pursuing a different strategy. Instead of relying on drugs that target individual cancer-related processes, their approach uses microRNAs, small pieces of genetic material capable of suppressing the activity of multiple problematic genes at the same time. By disrupting several genes that help glioblastoma grow and survive, the treatment could potentially slow or even stop tumor growth.
Getting these genetic molecules into the brain presents another major challenge. To overcome it, Abounader’s team uses focused ultrasound guided by magnetic resonance imaging (MRI), allowing researchers to direct sound waves precisely toward the intended area. The ultrasound works with tiny microbubbles to temporarily open the blood-brain barrier. This creates a brief opportunity for nanoparticles carrying the microRNAs to pass through the barrier and enter the brain, where they can act on genes involved in tumor growth.
Experimental Results and Future Trials
The researchers tested this approach in laboratory experiments and animal models of glioblastoma. Their findings showed that the microRNA treatment slowed tumor growth and helped the animals survive longer. Although these results are encouraging, the strategy remains experimental and will require additional research before it can be evaluated in human patients.
“This new approach could help target numerous molecules that promote cancer growth, including those for which no drugs exist, at the same time to achieve better therapies,” said Abounader, a professor at UVA’s School of Medicine in the Department of Microbiology, Immunology and Cancer Biology. “We are hoping to translate our findings into future clinical trials for patients with glioblastoma and other brain tumors.”
UVA Health has been at the forefront of focused ultrasound research since the technology’s early development. Over the years, its scientists have built an extensive research program investigating how precisely directed sound waves might be used to treat a wide range of medical conditions. Recognizing the technology’s potential in cancer care, UVA partnered with the Charlottesville-based Focused Ultrasound Foundation to establish the Focused Ultrasound Immuno-Oncology (FUSION) Center. It is the first center in the world devoted specifically to investigating how focused ultrasound can be combined with cancer immunotherapy.
The study was published in the Journal of Clinical Investigation. The research team included Shekhar Saha, Ying Zhang, Myron K. Gibert Jr., and other colleagues. The researchers reported having no financial interest in the work. Funding came from the National Institutes of Health’s National Cancer Institute and the National Institute of Neurological Disorders and Stroke, along with support from the Schiff Foundation, the Ben and Catherine Ivy Foundation, and the Focused Ultrasound Foundation.
Source: ScienceDaily
