NCI-funded Glioblastoma Therapeutics Network (GTN)
Despite enormous public and private investments into basic, translational, and clinical research for adult glioblastoma (GBM), treatment has not changed significantly in nearly 20 years. With the standard of care, the median survival is about 15 months, and 5-year survival is less than 5%.
There is an urgent need to improve the treatment of adult GBM by developing novel effective agents that can cross the blood-brain-barrier (BBB) and testing them in the clinic.
Challenges to Progress
- Since GBM infiltrates the brain locally and does not have a well-defined border, surgical removal of the tumor cannot obtain a tumor-free margin; therefore, adjuvant chemotherapy and radiation therapy (RT) after surgery are critical to treatment success.
- Chemotherapy must cross the BBB to have a therapeutic effect.
- RT dose is limited by damage to the nearby normal brain tissue.
- Because GBM tumor cells are genetically heterogenous and exist in an immunosuppressive tumor microenvironment, the efficacy of other therapies (e.g., targeted agents and immunotherapy) is impeded.
Network Purpose
The intention of the GTN U19 grants (RFA-CA-20-047) is to improve the treatment of adult GBM by developing novel effective agents that can cross the BBB and testing them in the clinic.
Network Goals
Highly collaborative U19 teams will drive therapeutic agent(s) from pre-clinical development, through IND studies, into pilot clinical studies in humans. Members cooperate between teams so that reagents, assay protocols, animal models, patient samples, technologies, and development of clinical protocols are shared.
Read a 2023 NCI staff publication for more details on the goals of the network.
Network Structure
- Each U19 team includes
- investigators from two or more institutions, two of which are capable of independently accruing patients with GBM to GTN clinical trials
- an Administrative Core
- at least two Research Projects
- at least one Shared Resources Core that serves at least one Research Project
- An independent Network Coordination Center provides network harmonization on scientific and clinical activities.
- A Steering Committee establishes criteria to move an agent into clinical trials and determines the readiness of GBM therapeutic candidates from the GTN or from other NIH programs to enter clinical studies.
Funded Projects
| Institutions | PI(s) | Grant Title |
|---|---|---|
|
UCSF Northwestern |
Butowski Stupp |
Advancing treatment and understanding of immunotherapy in glioblastoma |
| Brigham and Women's Hospital | Batchelor | Harvard/Stanford GTN Program: Novel targeted therapeutics for glioblastoma |
| City of Hope |
Portnow Badie |
Development of small molecule inhibitors and biologic agents for treatment of glioblastoma using intracerebral microdialysis and signatures of vulnerability |
|
Mayo Yale |
Sarkaria Galanis Bindra |
*Center of Innovation for Brain Tumor Therapeutics |
|
Duke University of Texas Southwestern |
Ashley Shay |
*U19 and Network Coordination Center
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