New diagnostic chip enables rapid monitoring of brain cancer treatment
· News-MedicalNew diagnostic chip pulls packets released from tumor cells out of blood, showing whether cancer cells died during chemotherapy infusion.
The effectiveness of chemotherapy for brain cancer, done with a technique that opens the blood-brain barrier, can be monitored by blood draw, researchers at Northwestern Medicine and the University of Michigan have shown.
The new test could help patients with a form of brain cancer called glioblastoma by informing doctors whether to continue with a particular chemotherapy drug, switch drugs or stop treatment. The study was primarily funded by the National Institutes of Health.
"Instead of waiting months, after one dose we can know if a given treatment is working," said Northwestern Medicine neurosurgeon Adam Sonaband, co-corresponding author of the study published in Nature Communications. "That is huge for glioblastoma patients. It could potentially prevent patients from getting prolonged treatments that are ineffective, thus also avoiding unnecessary side effects."
"There are tiny particles floating in patient blood, called extracellular vesicles, that have been released by the cancer cells. These particles act as messengers, carrying special bits of genetic tumor material and proteins. The big challenge is figuring out how to find and pull out only those that come from cancer cells and not from elsewhere in the body," said Sunitha Nagrath, the Dwight F. Benton Professor of Chemical Engineering at U-M and co-corresponding author of the study.
The Michigan team found a way to capture extracellular vesicles and particles (EVPs) from cancer cells with a specific lipid, or fat molecule, commonly found on the exosome's surface. Isolating them from blood plasma samples run through their GlioExoChip turns blood draws into "liquid biopsies."
EVPs from cells that die during treatments are easier to catch because the lipid used to capture the EVPs becomes more abundant. Therefore, the team counted the extracellular vesicles that came from tumors before and after each treatment, calculating a ratio by dividing the post-chemotherapy count by the pre-chemotherapy count. If that ratio was going up with each chemotherapy session, the treatment was successful. If it stayed flat or declined, the treatment was ultimately deemed unsuccessful.
"Opening the blood-brain barrier allows tumor-derived vesicles to be measured in blood, providing a clinically meaningful liquid biopsy signal," said Mark Youngblood, a neurosurgery resident at Northwestern Medicine and co-first author of the study. "The GlioExoChip provides a quick and minimally invasive way to monitor treatment response in a disease where MRI scans often give misleading results."
Additional support for this study was provided by the Lou and Jean Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Moceri Family Foundation, U-M Forbes Institute for Cancer Discovery, U.S. Department of Defense, American Brain Tumor Association, Tap Cancer Out and Focused Ultrasound Foundation. In-kind support was provided by Carthera, the manufacturer of the SonoCloud-9 device, an investigational product that is not yet approved outside clinical trials.
The device was built at the Lurie Nanofabrication Facility. The study was conducted with the help of the Michigan Center for Materials Characterization, Biointerfaces Institute Nanotechnicum and Proteomics Resource Facility.
The team has applied for patent protection with the assistance of U-M Innovation Partnerships and is seeking partners to bring the technology to market.
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