Therapeutic Targeting of the Blood-Brain Barrier in Pediatric Malignant Brain Tumors

Glioblastoma is an extremely aggressive brain tumor that has poor outcomes despite the use of multimodality therapy. Treatment options for malignant gliomas are significantly limited by the presence of the blood-brain barrier (BBB). The BBB is a protective element of the central nervous system that keeps toxins or pathogens circulating in the blood away from the brain. The protective nature of the BBB in turn also inhibits effective therapy from reaching tumor cells. The majority of agents used to combat high grade glioma growth have agents known to be able to cross the BBB. However, there are many agents that are effective against malignant glioma, but are not being utilized because they fail to cross the BBB. Due to this, there is a strong interest to enhance delivery of certain agents in hopes of improving survival rates of patients with malignant brain tumors. Additionally, the diversity in BBB integrity aids glioma stem cells (GSCs) in evading treatment, proliferating and developing treatment resistance, despite multi-modality therapy. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major contributing factor to tumor recurrence. The ultimate goal of this research is to enhance therapies targeting malignant tumor cells and their supportive BBB, in an effort to improve treatment response and prolong overall survival. The Children’s Brain Tumor Network provides researchers on this project access to a large database of samples they are not able to access elsewhere.