{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:50:12Z","timestamp":1791010212408,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tovorafenib"},{"name":"Day One Biopharmaceuticals, Inc"},{"name":"Physician Payments Sunshine Act"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a rare disease which is more often diagnosed in children and adolescents than adults. Activation of the MAPK\/ERK pathway is implicated in the majority of cases, and BRAF fusions are the most common genetic alteration. BRAF fusions result in dimerization and constitutive downstream MAPK\/ERK activity, against which type I RAF inhibitors have limited efficacy. Type II RAF inhibitors stabilize RAF in an inactive conformation and inhibit both dimer protomers, thus inhibiting downstream MAPK\/ERK activity in the setting of BRAF fusions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Presentation<\/jats:title>\n                  <jats:p>A previously-healthy 33 year old man was diagnosed with DL-GNT, which harbored a pathogenic BRAF:KIAA1549 gene fusion. He was initially treated with a MEK inhibitor but developed drug-related cardiotoxicity. Without treatment, he developed significant functional limitations due to leptomeningeal disease. A compassionate use indication was pursued for an investigational CNS-penetrant type II BRAF inhibitor, tovorafenib. Within 3 months of initiating the medication, the patient experienced notable gains in functional status and with over 12 months of treatment has been able to rejoin recreational activities.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This case highlights the importance of tumor molecular characterization, particularly in rare tumors, whereby identification of the BRAF:KIAA1594 gene fusion led to an appropriate selection of a type II BRAF inhibitor.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf093","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T12:54:11Z","timestamp":1747400051000},"source":"Crossref","is-referenced-by-count":3,"title":["Response to a novel type II RAF inhibitor in diffuse leptomeningeal glioneuronal tumor with BRAF 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