Key Points
- Researchers have developed a new focused ultrasound—based method of liquid biopsy.
- When used with an innovative medical device for testing and analysis, physicians could soon quickly determine whether brain tumor treatments are working.
A collaborative team of researchers from Northwestern Medicine and the University of Michigan have developed a new focused ultrasound—based method of liquid biopsy that could help determine whether glioblastoma treatments are working. The technique was recently published in Nature Communications.
French manufacturer Carthera has been conducting clinical trials to test the use of their SonoCloud low-intensity therapeutic ultrasound device combined with microbubbles to temporarily open the BBB after the administration of chemotherapy in patients with glioblastoma. During one of these studies (NCT04528680), the investigators collected blood samples before, during, and after the BBB opening to determine whether the procedure would enable liquid biopsies – laboratory tests that can analyze blood, urine, or cerebrospinal fluid (among other substances) for signs of cancer – to provide treatment updates.
Adam M. Sonabend, MD, a neurosurgeon specializing in brain tumors and Director of Translational Neurooncology at Northwestern Medicine, who is the principal investigator of the clinical trial, worked alongside Mark Youngblood, MD, PhD, a neurosurgery resident at Northwestern, Nagrath Sunitha, PhD, the Dwight F. Benton Professor of Chemical Engineering at the University of Michigan, and Abha Kumari, a PhD student in chemical engineering at Michigan to analyze the liquid biopsy specimens. To do so, Dr. Nagrath’s laboratory developed a new medical device for this testing and analysis:the “GlioExoChip” was designed to capture tumor-derived exosomes from the blood. Exosomes are molecules that provide intercellular communication by transmitting proteins, lipids, RNA, and DNA between cells.
Together the team analyzed the blood samples from the clinical trial participants to determine whether there was a relationship between the exosome levels and tumor cell death as a potential biomarker for treatment response. They counted tumor biomarkers levels before and after each treatment for the first two cycles and then calculated the differences to measure treatment success.
As compared with healthy controls, distinct expression patterns were found in the exosomes from the blood of the patients with brain tumors. Furthermore, the exosome patterns changed in the patients who underwent the SonoCloud treatment followed by chemotherapy, and those changes correlated with overall survival.
“Instead of waiting months, after one dose we can know if a given treatment is working,” said Dr. Sonabend in Northwestern University’s press release. “That is huge for glioblastoma patients. It could potentially prevent patients from getting prolonged treatments that are ineffective, thus also avoid unnecessary side effects.”
“What makes this so exciting is the potential impact for patients,” said Suzanne LeBlang, MD, the Foundation’s director of clinical relationships. “A blood test following focused ultrasound–mediated BBB opening could tell us early whether a therapy is working, helping patients stay on effective treatments or move to better options sooner—when time matters most.”
Before being put into clinical use, the researchers will next need to conduct additional studies to validate these initial findings.
This study was funded by the National Institutes of Health (National Cancer Institute) with additional support from the Lou and Jean Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, the Moceri Family Foundation, the University of Michigan Forbes Institute for Cancer Discovery, the United States Department of Defense, the American Brain Tumor Association, Tap Out Cancer, and the Focused Ultrasound Foundation.
See Northwestern’s Press Release
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