New diagnostic chip enables rapid monitoring of brain tumor treatment

New diagnostic chip enables rapid monitoring of brain tumor treatment

New diagnostic chip pulls packets released by tumor cells from the blood and shows whether cancer cells died during chemotherapy infusion.

Researchers at Northwestern Medicine and the University of Michigan have shown that the effectiveness of chemotherapy for brain cancer, delivered using a technique that opens the blood-brain barrier, can be monitored by taking a blood sample.

The new test could help patients with a form of brain cancer called glioblastoma by informing doctors whether they should continue with a particular chemotherapy drug, change the drug or stop treatment. The study was funded primarily by the National Institutes of Health.

“Instead of having to wait months, we can know after one dose whether a particular treatment is working,” said Northwestern Medicine neurosurgeon Adam Sonaband, co-author of the study published in Nature Communications. "This is huge for glioblastoma patients. It could potentially prevent patients from receiving ineffective treatments for long periods of time, thereby also avoiding unnecessary side effects."

Glioblastoma is a frequently fatal disease with most patients dying within two years and only 10% of patients still alive after five years. The tumor arises from the brain and invades it, so it cannot be completely removed. Some remaining cancer cells remain after surgery and lead to the development of new tumors. And unlike other types of cancer, most chemotherapy drugs and cancer drugs cannot cross the blood-brain barrier, which protects the brain from toxins.

Researchers at the Northwestern Medicine Malnati Brain Tumor Institute conducted an earlier clinical trial using Carthera's SonoCloud-9 in Lyon, France - a therapeutic ultrasound device that opened the blood-brain barrier for about an hour to allow the chemotherapy drug paclitaxel to enter. This new analysis, testing diagnostic technology from the University of Michigan, shows that the opening of the blood-brain barrier also allows tumor contents to leak into the blood. Blood samples taken before and after each treatment can be used to assess how well a treatment is working.

Tiny particles called extracellular vesicles, released by the cancer cells, float in the patient's blood. These particles act as messenger substances and transport specific parts of genetic tumor material and proteins. The big challenge is figuring out how to find and extract only those that come from cancer cells and not from other parts of the body.”

Sunitha Nagrath, Dwight F. Benton Professor of Chemical Engineering at UM and co-author of the study

The Michigan team found a way to capture extracellular vesicles and particles (EVPs) from cancer cells using a specific lipid, or fat molecule, commonly found on the surface of the exosome. By isolating from blood plasma samples run through their GlioExoChip, blood draws become “liquid biopsies.”

"Cells use extracellular vesicles and particles for communication, and EVPs can be misused for disease progression. It is exciting to be part of this technology that can successfully use EVPs to monitor treatment response in tumors," said Abha Kumari, a Ph.D. student in chemical engineering at UM and co-first author of the study.

EVPs from cells that die during treatment are easier to capture because the lipid used to capture the EVPs is more abundant. So the team counted the extracellular vesicles that came from tumors before and after each treatment and calculated a ratio by dividing the post-chemotherapy count by the pre-chemotherapy count. If this ratio increased with each chemotherapy session, the treatment was successful. If the value remained unchanged or decreased, the treatment was ultimately considered unsuccessful.

“Opening the blood-brain barrier allows measurement of tumor-derived vesicles in the 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 rapid and minimally invasive way to monitor treatment response in a disease where MRI scans often produce misleading results.”

Next, the researchers will validate their results with other glioblastoma therapies and continue to study the utility of detecting extracellular vesicles to assess treatment of other cancers.

Additional support for this study was provided by the Lou and Jean Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, the Moceri Family Foundation, the UM Forbes Institute for Cancer Discovery, the U.S. Department of Defense, the American Brain Tumor Association, Tap Cancer Out, and the Focused Ultrasound Foundation. In-kind support was provided by Carthera, the manufacturer of the SonoCloud-9 device, an investigational device not yet approved outside of clinical trials.

Carthera researchers also contributed to this study.

The device was built at the Lurie Nanofabrication Facility. The study was conducted with the help of the Michigan Center for Materials Characterization, the Biointerfaces Institute Nanotechnicum, and the Proteomics Resource Facility.

The team has applied for patent protection with support from UM Innovation Partnerships and is looking for partners to bring the technology to market.

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