DIPG is the most common brainstem tumor in children and is uniformly fatal. The BBB is intact in DIPG and plays an active role in restricting the delivery of systemically administered therapies into the tumor. Recent studies have shown that SHH signalling plays a major role in the maintenance of BBB integrity and this pathway is highly active in DIPG. We hypothesized that SHH signalling in DIPG plays a critical role in maintaining BBB integrity. Primary DIPG PDX (patient derived xenografts) secretes significantly higher quantities (~2-fold) of SHH compared to astrocytes and human brain microvascular endothelial cells (hBMVECs), (ELISA, P-value 750-fold increase in mRNA) when compared to astrocytes or endothelial cells, (qRT-PCR, P-value
