Decoding the biology of the blood-brain tumor barrier in brain cancer

Brain cancers are among the most lethal and challenging malignancies to treat in the clinic. An important impediment to effectively treat brain tumors is the blood-brain tumor barrier (BTB), an interface generated between the blood-brain barrier (BBB) and intra-cranial tumors, creating a tumor-permissive perivascular microenvironment. The BTB loses endothelial barrier properties in an heterogeneous manner across the tumor, but continues to impede effective intra-tumoral drug delivery, dramatically decreasing the potential of many anti-neoplastic pharmaceutics. This review will provide a summary of our current understanding of the molecular composition and cellular architecture of the BTB, focusing on glioblastoma and other high-grade gliomas. We will summarize different multi-omic and spatial studies performed with the goal to reveal unknown traits of the brain cancer-associated vasculature and identify molecular targets of therapeutic relevance. Our work aims to consolidate our current understanding of the vasculature in brain tumors, and the insights held regarding its role in brain cancer biology and therapeutic drug delivery.