The Blood-Brain Barrier in Brain Tumors: Molecular Mechanisms and Therapeutic Strategies

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Background

Despite of tremendous basic and clinical research in the field, the prognosis for most types of malignant primary and metastatic brain tumors are still dismal. In adults, glioma is the most common primary brain tumors in central nervous system with varying degrees of malignancy. Glioblastoma (GBM) is the most aggressive intracranial tumor and constitutes about 50% of all gliomas. The overall survival of GBM patients is only 15-18 months, and has not been improved substantially over the past three decades. In children, pediatric high-grade glioma (pHGG) is a group of primary malignant brain tumors with limited efficient treatment options. The prognosis for H3K27M mutant diffuse midline glioma, the most aggressive type of pHGG, is only one year. Brain metastases, arising in patients with different cancer subtypes, is one of the main cause of mortality in cancer patients. Extremely limited systematic therapeutic options after surgery and radiotherapy is one of the culprits for the dismal prognosis in brain tumor patients. For instance, there have been only four systemically administered blood-borne drugs approved by the FDA for GBM treatment.

The blood-brain barrier (BBB) is a specialization of brain endothelial cells (ECs), which hinders the effective delivery of drugs into the brain by establishing EC junctions, sealing EC-EC contacts, pumping the drugs out by active transports and suppressing transcytosis. Tumor vessels are abnormal and generally more permeable, with a heterogeneous and partially intact BBB. Brain tumors could be cured only when the tumor cells hidden behind the BBB are adequately treated. In-depth understanding of BBB regulation and its alterations in brain tumors is of great essence for overcoming the biological challenges imposed by the BBB and development of novel strategies for brain tumor treatment. Additionally, emerging novel glioma therapeutic approaches, such as immune therapy and glioma initiating cell-targeted therapy, represent newly unchartered territories awaiting extensive investigations in the perspective of cell-cell interactions with vascular endothelial cells.

This Research Topic aims at presenting the recent advances uncovering BBB regulation and its alterations in brain tumors, and how therapeutic strategies can be developed to deliver drug across the BBB to treat tumor cells. We welcome both original research and review articles within the scope of the research topic. Studies addressing following key points are of great interest under this the Research Topic:

1. Pathophysiological mechanisms underlying BBB alterations in glioma (including pediatric tumors) and brain metastatic tumors.

2. Advancements in the understanding of the cell heterogeneity and cell interactions (endothelial cells, pericytes, astrocytes, immune cells and tumor cells) of BBB components in both tumoral and non-tumoral conditions by single-cell sequencing.

3. Novel strategies to improve drug delivery across the BBB and brain penetration by perturbation of physiological/pathological BBB-regulating pathways; or by nanoparticle-mediated brain-targeted drug delivery systems; or by physical approaches, such as low-intensity focused ultrasound (FUS).

Please note that manuscripts applying only bioinformatics or computational approaches, due to the absence of experimental validation, will not be considered for this Research Topic.

Dr. Javad Rasouli is working in Spark Therapeutics as Immunology Scientist. This should not pose any conflict, and he will maintain objectivity.

Keywords: glioblastoma, vascular abnormality, blood-brain barrier, tumor angiogenesis

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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