Drug penetration in pediatric brain tumors: Challenges and opportunities

Larger clinical trial enrollments and a greater understanding of biological heterogeneity have led to improved survival rates for children diagnosed with brain tumors in the last 50 years. However, reducing long‐term morbidities and improving survival rates of high‐risk tumors remain major challenges. Chemotherapy can reduce tumor burden, but effective drug penetration at the tumor site is limited by barriers in the route of drug administration and within the tumor microenvironment. Bioavailability of drugs is impeded by the blood‐brain barrier, plasma protein binding, and structural components by the tumor including the matrix and vasculature contributing to increased interstitial fluid pressure, hypoxia, and acidity. Designing drug delivery systems to circumvent these barriers could lead to improved drug penetration at the tumor site and reduce adverse systemic side effects. In this review, we expand on how systemic and local barriers limit drug penetration and present potential methods to enhance drug penetration in pediatric brain tumors.