A new diagnostic chip developed by researchers at Northwestern Medicine and the University of Michigan enables doctors to quickly assess the effectiveness of chemotherapy for glioblastoma, a type of brain cancer. The device analyzes blood samples to determine whether tumor cells are dying during treatment, potentially allowing for faster adjustments to therapy.
Glioblastoma is an aggressive form of brain cancer with low survival rates. Most patients die within two years, and only about 10% survive five years after diagnosis. Surgery cannot fully remove the tumor due to its infiltration into brain tissue, and most chemotherapy drugs cannot cross the blood-brain barrier that protects the brain from toxins.
To address this challenge, researchers previously used a therapeutic ultrasound device called SonoCloud-9 from Carthera in Lyon, France, which temporarily opens the blood-brain barrier. This allows chemotherapy drugs such as paclitaxel to reach tumor cells. The new analysis shows that opening the barrier also lets tumor-derived particles enter the bloodstream, making it possible to monitor treatment response through simple blood draws.
"Instead of waiting months, after one dose we can know if a given treatment is working," said Adam Sonaband, neurosurgeon at Northwestern Medicine and 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."
The University of Michigan team developed a method to isolate extracellular vesicles and particles (EVPs) released by cancer cells using their GlioExoChip technology. These EVPs contain genetic material and proteins specific to tumors. By capturing them from blood plasma samples, doctors can perform "liquid biopsies" before and after each treatment session.
"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, professor of chemical engineering at U-M and co-corresponding author.
The researchers found that EVPs from dying tumor cells are easier to detect because they display more of a certain lipid on their surface—the target used for capture by GlioExoChip. They calculated a ratio between EVP counts before and after chemotherapy; an increasing ratio indicated effective treatment while a flat or declining ratio suggested otherwise.
"Cells use extracellular vesicles and particles for communication, and EVPs can be hijacked for disease progression. It is exciting to be a part of this technology that can successfully leverage EVPs for monitoring treatment response in tumors," said Abha Kumari, Ph.D. student at U-M and co-first author.
"Opening the blood-brain barrier allows tumor-derived vesicles to be measured in blood, providing a clinically meaningful liquid biopsy signal," said Mark Youngblood, neurosurgery resident at Northwestern Medicine and co-first author. "The GlioExoChip provides a quick and minimally invasive way to monitor treatment response in a disease where MRI scans often give misleading results."
The research was primarily funded by the National Institutes of Health with additional support from several organizations including 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; Focused Ultrasound Foundation; as well as Carthera which provided in-kind support with its investigational SonoCloud-9 device.
Researchers plan further validation with other glioblastoma therapies and will explore whether detecting extracellular vesicles could help assess treatments for other cancers as well.
Patent protection has been sought with assistance from U-M Innovation Partnerships as efforts continue toward bringing this technology to market.
