Faster Approach Determines Brain Cancer Treatment Is Working

Researchers at Northwestern Medicine – along with the University of Michigan – have developed a new and faster approach to determine if a treatment for the brain cancer glioblastoma is working.

Glioblastoma is universally lethal as neurosurgeons cannot remove all of the tumor cells and most drugs used for cancer can’t cross the blood-brain barrier into the brain to target the remaining cancer. This leads to leftover tumor cells surviving.

Northwestern Medicine Malnati Brain Tumor Institute researchers have previously done trials with the Sonocloud-9 device from Carthera in Lyon, France, a therapeutic ultrasound device that opens up the blood-brain barrier for about an hour so that chemotherapy can get in. But in a new analysis published in Nature Communications, Northwestern Medicine and University of Michigan researchers found that opening the blood-brain barrier lets tumor content leak into the blood, making it possible to test for brain cancer response to chemotherapy in the blood.

“Instead of removing tumor tissue, we analyzed blood for tumor material, known as extra-cellular vesicles or exosomes.” said Northwestern Medicine neurosurgeon Adam Sonabend, MD, one of the study’s authors. “Historically, that has not worked for brain tumors because of the blood-brain barrier posing a challenge for liquid biopsy for brain diseases.”

The researchers tested tiny particles released by the brain tumors - called extracellular vesicles (EVs) – that could be measured in the blood after temporarily opening the blood-brain barrier.

To do this, Northwestern Medicine researchers worked with University of Michigan researchers to develop a microfluidic chip called GlioExoChip that isolates tumor-derived exosomes and provides a minimally invasive way to monitor treatment response.

“Opening the blood-brain barrier allows tumor-derived vesicles to be measured in blood, providing a clinically meaningful liquid biopsy signal,” said Mark Youngblood, MD, PhD, a neurosurgery resident at Northwestern Medicine and co-lead 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.”

"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”, said Sunitha Nagrath, PhD, the Dwight F. Benton Professor of Chemical Engineering at the University of Michigan and co-corresponding author of the study. “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.”

The next steps for the researchers will be to validate their findings with other therapies and explore the potential to expand to other therapies.

“Instead of waiting months, after one dose we can know if a given treatment is working,” Dr. Sonabend said. “That is huge for glioblastoma patients. It could potentially prevent patients from getting prolonged treatments that are ineffective, thus also avoid unnecessary side effects.”

This study was primarily funded by the National Institutes of Health. Additional support for the study was provided by 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 Cancer Out and the Focused Ultrasound Foundation.