Focused ultrasound helped deliver microRNAs that targeted multiple glioblastoma genes and improved outcomes in animal models.
A treatment aimed at glioblastoma must first cross one of the body’s most selective defenses: the blood-brain barrier. Researchers at the University of Virginia Comprehensive Cancer Center are testing a way to briefly open that barrier and deliver genetic molecules capable of suppressing several drivers of the cancer at once.
The experimental strategy targets glioblastoma, the most common and deadliest form of brain cancer. Roger Abounader, MD, PhD, and his colleagues at UVA identified “microRNAs,” or miRNAs, that can reduce the activity of multiple malfunctioning genes involved in the tumor’s development and growth.
To carry those molecules into the brain, the researchers combine brain-penetrating nanoparticles with focused ultrasound and microscopic bubbles. The method is designed to move the miRNAs through the brain’s protective barrier, which usually prevents many treatments for tumors and neurodegenerative diseases from reaching their targets.
“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, Department of Microbiology Immunology and Cancer Biology, Comprehensive Cancer Center and Center for RNA Science and Medicine. “We are hoping to translate our findings into future clinical trials for patients with glioblastoma and other brain tumors.”
The blood-brain barrier blocks drugs
Glioblastoma is the most common and aggressive malignant brain tumor in adults and kills more than 13,000 people in the United States each year. Its cells spread through surrounding healthy brain tissue, making complete surgical removal extremely difficult.
Treatment is further complicated by the blood-brain barrier. This natural defense shields the brain from toxins and infections circulating in the bloodstream, but it also prevents many anti-tumor drugs from entering brain tissue.
Current care usually begins with surgery to remove as much of the tumor as possible. Doctors then use radiation and chemotherapy to extend survival, but the cancer remains exceptionally difficult to control.
MicroRNAs target several cancer genes
Abounader’s approach uses miRNAs, tiny pieces of genetic material that regulate gene activity. Delivering selected miRNAs could allow doctors to suppress several faulty genes simultaneously, slowing or stopping tumor growth by interfering with multiple biological pathways that sustain the cancer.
Conventional treatments struggle to accomplish the same task. Combining several cancer drugs can create harmful toxicity, and many of the molecules that promote glioblastoma growth do not have drugs capable of targeting them.
The researchers would deliver the miRNAs with focused ultrasound guided by magnetic resonance imaging (MRI). The concentrated sound waves direct tiny “microbubbles” to a specific location, temporarily opening the blood-brain barrier long enough for nanoparticles carrying the miRNAs to pass through.
Animal tests show early promise
In laboratory testing, the miRNA treatment slowed tumor growth and extended survival in animal models of glioblastoma. The approach will require additional study before it can be evaluated in people, but Abounader believes the findings support further investigation in glioblastoma and potentially other cancers.
“This approach could have broad applications for several brain and other human diseases,” Abounader said. “We and many others are intensively working to lighten the burden of cancer, and hopefully also completely cure it, but this requires a continued investment in cancer and medical research.”
Focused ultrasound expands cancer research
UVA Health was among the earliest institutions to explore focused ultrasound. Its experience with the technology has grown into a wider research program investigating how focused ultrasound might be used against a range of medical conditions.
UVA and the Charlottesville-based Focused Ultrasound Foundation also established the Focused Ultrasound Immuno-Oncology (FUSION) Center. It is the world’s first center devoted specifically to studying how focused ultrasound could be combined with cancer immunotherapy, an approach experts hope will improve cancer treatment.
Developing new forms of patient care is also a central goal of UVA Comprehensive Cancer Center and UVA’s Paul and Diane Manning Institute of Biotechnology. UVA Comprehensive Cancer Center is one of 57 centers in the United States to hold the National Cancer Institute’s “comprehensive” designation, which recognizes its cancer research and patient care.
The Manning Institute was created to speed the development of medicines and treatments for difficult diseases. A statewide clinical trials network complements that effort by expanding access to experimental treatments as they move through development and testing.
Reference: “Discovery and therapeutic delivery of microRNAs targeting deregulated glioblastoma pathways inhibits tumor growth in mice” by Shekhar Saha, Ying Zhang, Myron K. Gibert Jr., Collin Dube, Farina Hanif, Elizabeth Qian Xu Mulcahy, Sylwia Bednarek, Yunan Sun, Pawel Marcinkiewicz, Xiantao Wang, Gijung Kwak, Ahsan H. Polash, Haolin Li, Kadie Hudson, Manikarna Dinda, Tapas Saha, Matthew McCord, Fadila Guessous, Nichola Cruickshanks, Rossymar Rivera Colon, Lily Dell’Olio, Rajitha Anbu, Wenjie Liu, Songy Choi, Benjamin Kefas, Pankaj Kumar, Alexander L. Klibanov, David Schiff, Jung Soo Suk, Justin Hanes, Jamie Mata, Markus Hafner and Roger Abounader, 30 June 2026, The Journal of Clinical Investigation.
DOI: 10.1172/JCI195639
The research was supported by the National Institutes of Health’s National Cancer Institute, grants U01 CA220841 and P30 CA044579; the NIH’s National Institute of Neurological Disorders and Stroke, grants R01 NS122222 and R21 NS122136; a UVA Comprehensive Cancer Center pilot grant; a Schiff Foundation grant; the Ben and Catherine Ivy Foundation; and the Focused Ultrasound Foundation.
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