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Chemoradiation protocols have improved survival rates, even for non\u2010resectable tumors. Nonetheless, radiation therapy carries the risk of numerous adverse effects that can have long\u2010lasting, detrimental effects on the quality of life for survivors. The pursuit of chemotherapeutics that could obviate the need for radiotherapy remains ongoing. Several anti\u2010tumor agents, including sunitinib, valproic acid, carboplatin, and panobinostat, have shown effectiveness in various malignancies but have not proven effective in treating PBT. The presence of the blood\u2013brain barrier (BBB) plays a pivotal role in maintaining suboptimal concentrations of anti\u2010cancer drugs in the central nervous system (CNS). Ongoing research aims to modulate the integrity of the BBB to attain clinically effective drug concentrations in the CNS. However, current findings on the interaction of exogenous chemical agents with the BBB remain limited and do not provide a comprehensive explanation for the ineffectiveness of established anti\u2010cancer drugs in PBT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted our search for chemotherapeutic agents associated with the blood\u2013brain barrier (BBB) using the following keywords: Chemotherapy in Cancer, Chemotherapy in Brain Cancer, Chemotherapy in PBT, BBB Inhibition of Drugs into CNS, Suboptimal Concentration of CNS Drugs, PBT Drugs and BBB, and Potential PBT Drugs. We reviewed each relevant article before compiling the information in our manuscript. For the generation of figures, we utilized BioRender software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Focus<\/jats:title>\n                    <jats:p>We focused our article search on chemical agents for PBT and subsequently investigated the role of the BBB in this context. Our search criteria included clinical trials, both randomized and non\u2010randomized studies, preclinical research, review articles, and research papers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Finding<\/jats:title>\n                    <jats:p>Our research suggests that, despite the availability of potent chemotherapeutic agents for several types of cancer, the effectiveness of these chemical agents in treating PBT has not been comprehensively explored. Additionally, there is a scarcity of studies examining the role of the BBB in the suboptimal outcomes of PBT treatment, despite the effectiveness of these drugs for other types of tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.6647","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T20:35:15Z","timestamp":1700858115000},"page":"21075-21096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Chemotherapy in pediatric brain tumor and the challenge of the blood\u2013brain barrier"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5999-9187","authenticated-orcid":false,"given":"Johid Reza","family":"Malik","sequence":"first","affiliation":[{"name":"Antiviral Pharmacology Laboratory College of Pharmacy, University of Nebraska Medical Center  Omaha Nebraska 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