June 24, 2022
Mayo Clinic is helping to lead a national program to develop and test novel therapies for adults with glioblastoma. Funded by the National Cancer Institute (NCI), the Glioblastoma Therapeutics Network (GTN) is a U19 research program focused on driving therapeutic agents from preclinical development to pilot clinical studies.
"The neuro-oncology community is rethinking its approach to experimental glioblastoma therapies," says Ian F. Parney, M.D., Ph.D., a neurosurgeon at Mayo Clinic in Rochester, Minnesota. "Although glioblastoma absolutely has a better prognosis now than it had 20 years ago, other types of cancer have seen much more dramatic improvement."
Dr. Parney co-directs GTN's network coordination center, which harmonizes the group's scientific and clinical activities. The other co-director is Susan M. Geyer, Ph.D., a biostatistician at Mayo Clinic's campus in Minnesota.
GTN's work incorporates two main objectives:
- To determine that any potential treatment has some effect that crosses the blood-brain barrier before that treatment enters clinical trials
- To conduct phase 0 clinical trials to obtain preliminary information on safety and efficacy
"There is much greater awareness now of the importance of any potential treatment — whether it's a drug, a virus or a vaccine — being able to overcome the blood-brain barrier," Dr. Parney says. "We hope our approach will concentrate efforts on therapies that have a greater chance of helping patients. We want to do better for patients with glioblastoma — and do it sooner."
Collaboration to spur progress
The median survival for individuals with glioblastoma is about 15 months. In addition to the blood-brain barrier, other challenges to finding effective treatments include the genetic heterogeneity of glioblastoma tumor cells and the immunosuppressive tumor microenvironment.
GTN members share reagents, assay protocols, animal models, patient samples, technologies and the development of clinical protocols. In addition to Mayo Clinic, network members include the University of California San Francisco, Northwestern University, Harvard University, City of Hope, Yale University, Duke University and University of Texas Southwestern Medical Center.
Five grant proposals, each involving two or three different centers, are in preparation. Mayo Clinic's research proposal is a partnership with Yale University. "Collaboration is built into the process," Dr. Parney says.
GTN collaboration includes standardizing testing methods and biomarkers — an important step toward finding treatments that address the heterogeneity of glioblastoma cells.
"Choosing particular biomarkers to be used in each GTN study can help us figure out whether tumors with particular molecular expression patterns or immune expression patterns will respond to a type of treatment," Dr. Parney says. "We might be able to find something as simple as a blood or urine test that would tell us if we're getting the response we would expect, in which case we'll continue to develop that therapy."
Phase 0 clinical trials can further boost research efficiency. They might entail giving selected patients a novel therapy before tumor resection, then assessing during surgery the therapy's ability to reach tumors and have the desired effect.
"It doesn't make sense to go on to bigger studies without that information, particularly if you're using a therapy that has never been given to patients with glioblastoma," Dr. Parney says.
GTN research builds on Mayo Clinic's previous studies of brain tumor therapy. One effort involves using contrast MRI to understand the pharmacokinetics of cefazolin and levetiracetam, commonly given to patients before brain tumor surgery.
Cefazolin, which doesn't cross the blood-brain barrier, would be expected to reach only areas of the brain where the barrier is broken. Levetiracetam, which does cross the barrier, would be expected to reach areas both where the barrier is intact and where it's broken.
"In fact, we've seen that it's not so simple," Dr. Parney says. "The areas where we would think the blood-brain barrier would be broken down aren't completely broken down. Sometimes the medications don't get to where we think they should. We are developing a more nuanced understanding of how this process works in people with brain tumors and how we can model that in our clinical trials."
Dr. Parney notes the tremendous strides already made in brain tumor surgeries, radiation therapies, chemotherapies and targeted therapies. "Even patients with the most-aggressive brain tumors can do well for years after treatment," he says.
GTN's goal is to further boost that progress. "Pooling our resources of knowledge will help us to be smarter and tailor our treatments," Dr. Parney says. "It's an exciting time. We're getting onto the threshold of things that will really make a profound difference for even more patients."
For more information
Refer a patient to Mayo Clinic.