Exploring the relationship of transient blood-brain barrier disruption to inhibition of malignant glioma progression

One of the major obstacles to effectively treating central nervous system (CNS) tumors is the integrity of the blood-brain barrier (BBB). The BBB prevents systemic drug delivery from reaching the brain and brain tumor tissue. While previous studies have mainly focused on circumventing the BBB, very few agents or mechanisms have been explored that modulate the tumor microenvironment to enhance effective therapies for malignant brain tumors. Our studies focus on understanding the heterogeneity of BBB permeability amongst malignant tumor cells and the role of the supportive BBB in tumor growth. Our collaborative laboratory and clinical investigations center around BBB biology, cancer biology, pharmacokinetics and pharmacodynamics related to optimal CNS drug delivery.

Using a clinical/translational approach, we aim to:

1) Evaluate the efficacy of targeted tumor and BBB directed therapy

2) Define the mechanisms that drive differences in neuropharmacokinetics of agents to the CNS

3) Identify exquisite parameters via neuro-imaging of CNS permeability amongst malignant brain tumors.

Our overall goal is to enhance our understanding of the heterogeneity of blood-brain barrier permeability among tumor cells and develop mechanism-based therapeutic interventions to treat affected brain tumor patients at the NIH Clinical Center. We use a combination of cell biology, molecular biology, imaging, pharmacokinetics and animal tumor models.