{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:41:01Z","timestamp":1792532461349,"version":"4.5.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100006293","name":"American Society of Clinical Oncology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006293","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006098","name":"Radiological Society of North America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT). Successful implementation of radiosensitization strategies in DMG remains an essential and promising avenue of investigation. We explore the use of Napabucasin, an NAD(P)H quinone dehydrogenase 1 (NQO1)-bioactivatable reactive oxygen species (ROS)-inducer, as a potential therapeutic radiosensitizer in DMG.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, we conduct in vitro and in vivo assays using patient-derived DMG cultures to elucidate the mechanism of action of Napabucasin and its radiosensitizing properties. As penetration of systemic therapy through the blood-brain barrier (BBB) is a significant limitation to the success of DMG therapies, we explore focused ultrasound (FUS) and convection-enhanced delivery (CED) to overcome the BBB and maximize therapeutic efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Napabucasin is a potent ROS-inducer and radiosensitizer in DMG, and treatment-mediated ROS production and cytotoxicity are dependent on NQO1. In subcutaneous xenograft models, combination therapy with RT improves local control. After optimizing targeted drug delivery using CED in an orthotopic mouse model, we establish the novel feasibility and survival benefit of CED of Napabucasin concurrent with RT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>As nearly all DMG patients will receive RT as part of their treatment course, our validation of the efficacy of radiosensitizing therapy using CED to prolong survival in DMG opens the door for exciting novel studies of alternative radiosensitization strategies in this devastating disease while overcoming limitations of the BBB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae215","type":"journal-article","created":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T10:58:58Z","timestamp":1728730738000},"page":"795-810","source":"Crossref","is-referenced-by-count":8,"title":["Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-742X","authenticated-orcid":false,"given":"Matthew","family":"Gallitto","sequence":"first","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]},{"name":"Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Development, Institute for Cancer Genetics, Columbia University Irving Medical Center , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genesis","family":"De Los Santos","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Jian","family":"Wei","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University , Roanoke, 24016 ,","place":["USA"]},{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]},{"name":"Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester Calvo","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center , New York, New York ,","place":["USA"]},{"name":"Department of Systems Biology, Columbia University Irving Medical Center , New York, New York ,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard , Cambridge, Massachusetts ,","place":["USA"]},{"name":"Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoufu","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Genetics and Development, Institute for Cancer Genetics, Columbia University Irving Medical Center , New York, New York ,","place":["USA"]},{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing, 100101 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor J","family":"Kinslow","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]},{"name":"Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xander","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Tomassoni","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University 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