Structured review reveals age-dependent blood-brain barrier maturation and tumor barrier heterogeneity in pediatric brain tumors, highlighting mechanisms behind adult drug translation failures.
Pediatric brain tumors remain a leading cause of cancer-related mortality in children, partially due to ineffective delivery of systemic therapies across the blood-brain barrier (BBB). Unlike adults, the pediatric blood–brain barrier (BBB) in infants undergoes significant postnatal maturation during the first year of life, resulting in age-dependent differences in permeability, transporter expression, and barrier regulation. The project examines how BBB immaturity and blood-brain tumor barrier (BBTB) heterogeneity influence the delivery discrepancy, efficacy and toxicity of antitumor drugs (chemotherapy, targeted therapies, and radiation), and the development of emerging, novel antitumor drug delivery tools for infantile brain tumors. This review distinguishes between the developing physiological BBB and the pathological BBTB, which may exhibit regionally increased or decreased permeability depending on tumor biology. Through a structured review of current literature, the study aims to identify why therapeutic strategies for adult brain tumor patients fail to translate to pediatric brain tumor populations and highlight clinical implications of the BBB in drug resistance, toxicity, and therapeutic design.
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Madeleine Yang (2026) studied this question.
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