{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:24Z","timestamp":1787027904402,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Pediatric gliomas encompass the most common brain tumor in children and are subdivided into pediatric low-grade gliomas (pLGGs) and pediatric high-grade gliomas (pHGGs). The era of molecular diagnosis has shifted the treatment paradigms and management of these patients. RAS\/MAPK pathway alterations serve as the driver in the majority of pLGGs, a subset of pHGG and NF1-related plexiform neurofibromas (PNs). The role of small molecule inhibitors in the treatment of these tumors has evolved in the past decade, facilitated through multiple clinical trials and moving into earlier stages of treatment. Although these developments hold promise, questions remain regarding targeted therapy, the long-term toxicities, the duration of treatment and the potential effects on the natural history of the tumor behavior.<\/jats:p>","DOI":"10.3390\/curroncol32050280","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:39:16Z","timestamp":1747283956000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Precision Medicine for Pediatric Glioma and NF1-Associated Tumors: The Role of Small Molecule Inhibitors"],"prefix":"10.3390","volume":"32","author":[{"given":"Samuele","family":"Renzi","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, CHU de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0E8, Canada"},{"name":"Department of Pediatrics, CHU de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0E8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bennett","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Toronto, ON M5G 1E8, Canada"},{"name":"Arthur and Sonia Labatt Brain Tumour Research Center, Toronto, ON M5G 0A4, Canada"},{"name":"Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirav","family":"Thacker","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Children\u2019s Hospital of Eastern Ontario (CHEO), Ottawa, ON K1H 8M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-8956","authenticated-orcid":false,"given":"Chantel","family":"Cacciotti","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, London Health Sciences Centre & Western University, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"v1","DOI":"10.1093\/neuonc\/nox158","article-title":"CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010\u20132014","volume":"19","author":"Ostrom","year":"2017","journal-title":"Neuro Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1200\/JCO.2008.21.2738","article-title":"Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: Prospective evaluation of cognitive, endocrine, and hearing deficits","volume":"27","author":"Merchant","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1200\/JCO.1993.11.5.850","article-title":"Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood","volume":"11","author":"Packer","year":"1993","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.ccell.2020.03.011","article-title":"Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas","volume":"37","author":"Ryall","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40478-020-00902-z","article-title":"Pediatric low-grade glioma in the era of molecular diagnostics","volume":"8","author":"Ryall","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S1470-2045(19)30277-3","article-title":"Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: A multicentre, phase 2 trial","volume":"20","author":"Fangusaro","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1093\/neuonc\/noab047","article-title":"A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: A Pediatric Brain Tumor Consortium study","volume":"23","author":"Fangusaro","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1200\/JCO.22.01000","article-title":"Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric","volume":"41","author":"Bouffet","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1056\/NEJMoa2303815","article-title":"Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations","volume":"389","author":"Bouffet","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Perreault, S., Larouche, V., Tabori, U., Hawkin, C., Lipp\u00e9, S., Ellezam, B., D\u00e9carie, J.C., Th\u00e9oret, Y., M\u00e9tras, M., and Sultan, S. (2019). A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK\/ERK pathway: TRAM-01. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6442-2"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"i191","DOI":"10.1093\/neuonc\/noac079.716","article-title":"LTBK-04. LATE BREAKING ABSTRACT: MEK162 (binimetinib) in children with progressive or recurrent low-grade glioma: A multi-institutional phase II and target validation study","volume":"24","author":"Robison","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s11523-022-00888-9","article-title":"Cobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I\/II Study","volume":"17","author":"Trippett","year":"2022","journal-title":"Target. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.1158\/1078-0432.CCR-19-2177","article-title":"Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation\u2013Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I\/IIa Study","volume":"25","author":"Hargrave","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.18632\/oncotarget.27600","article-title":"Phase I study of vemurafenib in children with recurrent or progressive BRAF","volume":"11","author":"Nicolaides","year":"2020","journal-title":"Oncotarget"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Del Bufalo, F., Ceglie, G., Cacchione, A., Alessi, I., Colafati, G.S., Carai, A., Diomedi-Camassei, F., De Billy, E., Agolini, E., and Mastronuzzi, A. (2018). V600E Inhibitor (Vemurafenib) for BRAF V600E Mutated Low Grade Gliomas. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00526"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1200\/PO.19.00298","article-title":"Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition","volume":"4","author":"Nobre","year":"2020","journal-title":"JCO Precis. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41591-023-02668-y","article-title":"The type II RAF inhibitor tovorafenib in relapsed\/refractory pediatric low-grade glioma: The phase 2 FIREFLY-1 trial","volume":"30","author":"Kilburn","year":"2024","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"van Tilburg, C.M., Kilburn, L.B., Perreault, S., Schmidt, R., Azizi, A.A., Cruz-Mart\u00ednez, O., Z\u00e1potock\u00fd, M., Scheinemann, K., Meeteren, A.Y.N.S., and Sehested, A. (2024). LOGGIC\/FIREFLY-2: A phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-11820-x"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"de la Fuente, M., Butowski, N.A., Taylor, J., Yaeger, R., Tsai, F.Y.C., Janku, F., Allen, C.E., Ammakkanavar, N., Michelson, G., and Jiang, P. (2024). TRLS-02. SAFETY AND EFFICACY OF BRAF INHIBITOR PLIXORAFENIB (FORE8394; PLX8394) IN CHILDREN AND ADULTS WITH RECURRENT, BRAF-ALTERED PRIMARY CENTRAL NERVOUS SYSTEM TUMORS (PCNST). Neuro Oncol., 26.","DOI":"10.1093\/neuonc\/noae064.155"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1093\/neuonc\/nou059","article-title":"Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas","volume":"16","author":"Karajannis","year":"2014","journal-title":"Neuro Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e28787","DOI":"10.1002\/pbc.28787","article-title":"A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma","volume":"68","author":"Wright","year":"2021","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1158\/1078-0432.CCR-24-0581","article-title":"Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions","volume":"31","author":"Lamoureux","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1093\/neuonc\/noac087","article-title":"Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)","volume":"24","author":"Desai","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10007","DOI":"10.1200\/JCO.2023.41.16_suppl.10007","article-title":"Erdafitinb in patients with FGFR-altered tumors: Results from the NCI-COG Pediatric MATCH trial arm B (APEC1621B)","volume":"41","author":"Lee","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S1470-2045(23)00275-9","article-title":"Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): An international, single-arm, phase 2 study","volume":"24","author":"Pant","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1093\/neuonc\/noab274","article-title":"Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors","volume":"24","author":"Doz","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/neuonc\/now282","article-title":"A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: A Pediatric Brain Tumor Consortium (PBTC) study","volume":"19","author":"Banerjee","year":"2017","journal-title":"Neuro Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"vdae036","DOI":"10.1093\/noajnl\/vdae036","article-title":"Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas","volume":"6","author":"Viskochil","year":"2024","journal-title":"Neuro Oncol. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1056\/NEJMoa1904059","article-title":"Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma","volume":"381","author":"Robert","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/S1470-2045(17)30679-4","article-title":"Dabrafenib plus trametinib in patients with previously untreated BRAF","volume":"18","author":"Planchard","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1200\/JCO.2017.73.6785","article-title":"Dabrafenib and Trametinib Treatment in Patients with Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer","volume":"36","author":"Subbiah","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jtho.2021.08.011","article-title":"Phase 2 Study of Dabrafenib Plus Trametinib in Patients with BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis","volume":"17","author":"Planchard","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.annonc.2021.12.014","article-title":"Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: Updated analysis from the phase II ROAR basket study","volume":"33","author":"Subbiah","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1080\/17460441.2020.1746265","article-title":"The discovery and development of binimetinib for the treatment of melanoma","volume":"15","author":"Tran","year":"2020","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Robinson, G.W., Vinitsky, A., Bag, A.K., Chiang, J., Li, Q., Lin, T., Hoehn, M.E., Edwards, A., Storment, D., and Singh, A. (2024). LGG-53. RESULTS FROM THE PHASE 1 AND PHASE 1 EXPANSION COHORTS OF SJ901: A PHASE 1\/2 TRIAL OF SINGLE-AGENT MIRDAMETINIB (PD-0325901) IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH LOW-GRADE GLIOMA. Neuro Oncol., 26.","DOI":"10.1093\/neuonc\/noae064.443"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7294","DOI":"10.1158\/1078-0432.CCR-17-3572","article-title":"A Phase I and Pharmacokinetic Study of Oral Dabrafenib in Children and Adolescent Patients with Recurrent or Refractory","volume":"25","author":"Kieran","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.3390\/curroncol31070299","article-title":"Canadian Consensus for Treatment of BRAF","volume":"31","author":"Erker","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1093\/neuonc\/noae074","article-title":"Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions-International Pediatric Low-Grade Glioma Coalition","volume":"26","author":"Cooney","year":"2024","journal-title":"Neuro Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10002","DOI":"10.1200\/JCO.2024.42.16_suppl.10002","article-title":"Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial","volume":"42","author":"Witt","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1212\/WNL.0000000000203833","article-title":"Pemigatinib For Previously Treated Central Nervous System Tumors With Activating FGFR Mutations or Translocations: Results From FIGHT-207 (S17.004)","volume":"100","author":"Spanggaard","year":"2023","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41379-018-0118-3","article-title":"Molecular characterization of cancers with NTRK gene fusions","volume":"32","author":"Gatalica","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1470-2045(18)30119-0","article-title":"Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: Phase 1 results from a multicentre, open-label, phase 1\/2 study","volume":"19","author":"Laetsch","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1158\/1078-0432.CCR-21-3597","article-title":"Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors","volume":"28","author":"Demetri","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1-2 trials","volume":"21","author":"Doebele","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/S1470-2045(18)30649-1","article-title":"Lorlatinib in patients with ALK-positive non-small-cell lung cancer: Results from a global phase 2 study","volume":"19","author":"Solomon","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100857","DOI":"10.1016\/j.neo.2022.100857","article-title":"Pediatric low-grade glioma: Targeted therapeutics and clinical trials in the molecular era","volume":"36","author":"Manoharan","year":"2023","journal-title":"Neoplasia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1200\/JCO.23.01838","article-title":"Everolimus for Children with Recurrent or Progressive Low-Grade Glioma: Results from the Phase II PNOC001 Trial","volume":"42","author":"Aboian","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1093\/neuonc\/noaa071","article-title":"A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1-associated pediatric low-grade glioma: A Neurofibromatosis Clinical Trials Consortium study","volume":"22","author":"Ullrich","year":"2020","journal-title":"Neuro Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/s13023-023-02982-1","article-title":"Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice","volume":"18","author":"Cockerell","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1056\/NEJMoa1001671","article-title":"Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis","volume":"363","author":"Krueger","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/ana.24523","article-title":"Everolimus for subependymal giant cell astrocytoma: 5-year final analysis","volume":"78","author":"Franz","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/S0140-6736(18)31791-4","article-title":"Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG\/NOA-09): A randomised, open-label, phase 3 trial","volume":"393","author":"Herrlinger","year":"2019","journal-title":"Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/neuonc\/noq191","article-title":"Temozolomide in the treatment of high-grade gliomas in children: A report from the Children\u2019s Oncology Group","volume":"13","author":"Cohen","year":"2011","journal-title":"Neuro Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00401-011-0802-6","article-title":"Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma","volume":"121","author":"Schindler","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ccell.2017.08.017","article-title":"Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma","volume":"32","author":"Mackay","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00401-015-1405-4","article-title":"Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers","volume":"129","author":"Korshunov","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1200\/JCO.21.02840","article-title":"Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial","volume":"40","author":"Eckstein","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10505","DOI":"10.1200\/JCO.2018.36.15_suppl.10505","article-title":"Dabrafenib in pediatric patients with BRAF\/ V600\u2013positive high-grade glioma (HGG)","volume":"36","author":"Hargrave","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5174","DOI":"10.1200\/JCO.23.00558","article-title":"Phase II Trial of Dabrafenib Plus Trametinib in Relapsed\/Refractory","volume":"41","author":"Hargrave","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1093\/neuonc\/noac096","article-title":"Upfront molecular targeted therapy for the treatment of BRAF-mutant pediatric high-grade glioma","volume":"24","author":"Rosenberg","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1158\/1078-0432.CCR-21-3382","article-title":"BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I\/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma","volume":"28","author":"Mehnert","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/CMR.0000000000000821","article-title":"A lead-in safety study followed by a phase 2 clinical trial of dabrafenib, trametinib and hydroxychloroquine in advanced BRAFV600 mutant melanoma patients previously treated with BRAF-\/MEK-inhibitors and immune checkpoint inhibitors","volume":"32","author":"Awada","year":"2022","journal-title":"Melanoma Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1158\/2159-8290.CD-14-0049","article-title":"Autophagy inhibition improves chemosensitivity in BRAF(V600E) brain tumors","volume":"4","author":"Levy","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"104686","DOI":"10.1016\/j.phrs.2020.104686","article-title":"A unique CDK4\/6 inhibitor: Current and future therapeutic strategies of abemaciclib","volume":"156","author":"Chong","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.ccell.2024.08.006","article-title":"GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant","volume":"42","author":"Liu","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.2147\/OTT.S149245","article-title":"Profile of abemaciclib and its potential in the treatment of breast cancer","volume":"11","author":"Martin","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6317","DOI":"10.18632\/oncotarget.27238","article-title":"Central nervous system-specific efficacy of CDK4\/6 inhibitors in randomized controlled trials for metastatic breast cancer","volume":"10","author":"Nguyen","year":"2019","journal-title":"Oncotarget"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1158\/1078-0432.CCR-20-1764","article-title":"A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer","volume":"26","author":"Tolaney","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1002\/cai2.143","article-title":"Beyond clinical trials: CDK4\/6 inhibitor efficacy predictors and nomogram model from real-world evidence in metastatic breast cancer","volume":"3","author":"Liu","year":"2024","journal-title":"Cancer Innov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"vi72","DOI":"10.1093\/neuonc\/noab196.280","article-title":"CTNI-55. THE CDK4\/6 INHIBITOR ABEMACICLIB IN PATIENTS WITH RECURRENT MENINGIOMA AND OTHER PRIMARY CNS TUMORS","volume":"23","author":"Coffee","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s11060-020-03641-2","article-title":"A phase I\/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG)","volume":"149","author":"DeWire","year":"2020","journal-title":"J. Neurooncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1158\/1078-0432.CCR-20-4078","article-title":"A Phase I and Surgical Study of Ribociclib and Everolimus in Children with Recurrent or Refractory Malignant Brain Tumors: A Pediatric Brain Tumor Consortium Study","volume":"27","author":"DeWire","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1158\/1078-0432.CCR-19-0133","article-title":"A Phase 0 Trial of Ribociclib in Recurrent Glioblastoma Patients Incorporating a Tumor Pharmacodynamic- and Pharmacokinetic-Guided Expansion Cohort","volume":"25","author":"Tien","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s43018-021-00198-5","article-title":"Palbociclib demonstrates intracranial activity in progressive brain metastases harboring cyclin-dependent kinase pathway alterations","volume":"2","author":"Brastianos","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Young, J.S., Kidwell, R.L., Zheng, A., Haddad, A.F., Aghi, M.K., Raleigh, D.R., Schulte, J.D., and Butowski, N.A. (2022). CDK 4\/6 inhibitors for the treatment of meningioma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.931371"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1758835918793326","article-title":"Management of adverse events during cyclin-dependent kinase 4\/6 (CDK4\/6) inhibitor-based treatment in breast cancer","volume":"10","author":"Thill","year":"2018","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e029361","DOI":"10.1161\/JAHA.123.029361","article-title":"Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4\/6 Inhibitors in Patients With Metastatic Breast Cancer","volume":"12","author":"Fradley","year":"2023","journal-title":"J. Am. Heart Assoc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ajmg.a.33139","article-title":"Birth incidence and prevalence of tumor-prone syndromes: Estimates from a UK family genetic register service","volume":"152A","author":"Evans","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1215\/15228517-2008-011","article-title":"Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1","volume":"10","author":"Mautner","year":"2008","journal-title":"Neuro Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1093\/neuonc\/noy067","article-title":"Association of plexiform neurofibroma volume changes and development of clinical morbidities in neurofibromatosis 1","volume":"20","author":"Gross","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ikuta, K., Nishida, Y., Sakai, T., Koike, H., Ito, K., Urakawa, H., and Imagama, S. (2022). Surgical Treatment and Complications of Deep-Seated Nodular Plexiform Neurofibromas Associated with Neurofibromatosis Type 1. J. Clin. Med., 11.","DOI":"10.3390\/jcm11195695"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1200\/JCO.20.02220","article-title":"NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas","volume":"39","author":"Weiss","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-020-01193-6","article-title":"Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: A phase 2 trial","volume":"27","author":"Fisher","year":"2021","journal-title":"Nat. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/neuonc\/noad086","article-title":"Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1\/2 trial for inoperable plexiform neurofibromas","volume":"25","author":"Gross","year":"2023","journal-title":"Neuro Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/neuonc\/noac109","article-title":"Selumetinib in children with neurofibromatosis type 1 and asymptomatic inoperable plexiform neurofibroma at risk for developing tumor-related morbidity","volume":"24","author":"Gross","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1056\/NEJMoa1605943","article-title":"Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas","volume":"375","author":"Dombi","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1912735","article-title":"Selumetinib in Children with Inoperable Plexiform Neurofibromas","volume":"382","author":"Gross","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"iii420","DOI":"10.1093\/neuonc\/noaa222.619","article-title":"NFB-17. MEK INHIBITOR BINIMETINIB SHOWS CLINICAL ACTIVITY IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1- ASSOCIATED PLEXIFORM NEUROFIBROMAS: A REPORT FROM PNOC AND THE NF CLINICAL TRIALS CONSORTIUM","volume":"22","author":"Mueller","year":"2020","journal-title":"Neuro Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1200\/JCO.24.01034","article-title":"ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma","volume":"43","author":"Moertel","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3171\/jns.1997.86.5.0747","article-title":"Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas","volume":"86","author":"Packer","year":"1997","journal-title":"J. Neurosurg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1200\/JCO.2011.36.6054","article-title":"Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: A report from the Children\u2019s Oncology Group","volume":"30","author":"Ater","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1053\/j.seminoncol.2013.09.013","article-title":"Therapy-related myelodysplasia and acute myeloid leukemia","volume":"40","author":"Bhatia","year":"2013","journal-title":"Semin. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e248","DOI":"10.1097\/MPH.0000000000001427","article-title":"Trametinib Toxicities in Patients With Low-grade Gliomas and Diabetes Insipidus: Related Findings?","volume":"42","author":"Egan","year":"2020","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1056\/NEJMoa2308849","article-title":"Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma","volume":"389","author":"Loriot","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Kommalapati, A., Tella, S.H., Borad, M., Javle, M., and Mahipal, A. (2021). FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice. Cancers, 13.","DOI":"10.3390\/cancers13122968"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e30410","DOI":"10.1002\/pbc.30410","article-title":"Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients","volume":"70","author":"Fischer","year":"2023","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.annonc.2020.06.010","article-title":"TRK inhibitors: Managing on-target toxicities","volume":"31","author":"Lim","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Liguori, V., Gaio, M., Zinzi, A., Cagnotta, C., Riccardi, C., Docimo, G., and Capuano, A. (2023). The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092538"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"100087","DOI":"10.1016\/j.esmoop.2021.100087","article-title":"The European Medicines Agency review of entrectinib for the treatment of adult or paediatric patients with solid tumours who have a neurotrophic tyrosine receptor kinase gene fusions and adult patients with non-small-cell lung cancer harbouring ROS1 rearrangements","volume":"6","author":"Delgado","year":"2021","journal-title":"ESMO Open"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3892\/ijo.2021.5234","article-title":"Everolimus therapy and side-effects: A systematic review and meta-analysis","volume":"59","author":"Arena","year":"2021","journal-title":"Int. J. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10549-013-2630-y","article-title":"Everolimus: Side effect profile and management of toxicities in breast cancer","volume":"140","author":"Paplomata","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1513\/AnnalsATS.201309-332LE","article-title":"Everolimus-induced severe pulmonary toxicity with diffuse alveolar hemorrhage","volume":"10","author":"Junpaparp","year":"2013","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1200\/JCO.2024.42.16_suppl.2055","article-title":"Cost-effectiveness of dabrafenib plus trametinib in BRAFV600E-mutant pediatric low-grade glioma: A microsimulation study","volume":"42","author":"Gascon","year":"2024","journal-title":"J. Clin. Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/5\/280\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:32:55Z","timestamp":1760031175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/5\/280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":104,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["curroncol32050280"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32050280","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]}}}