Addressing blood-brain-tumor-barrier heterogeneity in pediatric brain tumors with innovative preclinical models

• Published in: Frontiers in oncology Vol. 13; p. 1101522
• Main Authors: Morris, Elysse K, Daignault-Mill, Sheena, Stehbens, Samantha J, Genovesi, Laura A, Lagendijk, Anne K
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 26.01.2023
• Subjects: blood brain barrier; endothelial cells; medulloblastoma; neurovascular unit; Oncology; pediatric brain tumor; zebrafish; blood brain barrier; endothelial cells; medulloblastoma; zebrafish; pediatric brain tumor; microfluidics; neurovascular unit
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2023.1101522

Brain tumors represent the leading cause of disease-related mortality and morbidity in children, with effective treatments urgently required. One factor limiting the effectiveness of systemic therapy is the blood-brain-barrier (BBB), which limits the brain penetration of many anticancer drugs. BBB integrity is often compromised in tumors, referred to as the blood-brain-tumor-barrier (BBTB), and the impact of a compromised BBTB on the therapeutic sensitivity of brain tumors has been clearly shown for a few selected agents. However, the heterogeneity of barrier alteration observed within a single tumor and across distinct pediatric tumor types represents an additional challenge. Herein, we discuss what is known regarding the heterogeneity of tumor-associated vasculature in pediatric brain tumors. We discuss innovative and complementary preclinical model systems that will facilitate real-time functional analyses of BBTB for all pediatric brain tumor types. We believe a broader use of these preclinical models will enable us to develop a greater understanding of the processes underlying tumor-associated vasculature formation and ultimately more efficacious treatment options.