{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:43:37Z","timestamp":1790837017826,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Pediatric low-grade gliomas (pLGG) are a group of tumors largely driven by alterations in a single genetic pathway, known as the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway. Recent biologic insights and therapeutic targeting of MAPK-alterations have dramatically shifted the treatment approach in pLGG. While chemotherapy remains front-line therapy for unresectable pLGG in most scenarios (with the notable exception of\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600E<\/jats:sup>\n                    -altered tumors), many patients recur following cytotoxic agents and require further treatment. Inhibitors of the MAPK pathway, primarily MEK and RAF kinase inhibitors, have emerged as effective and tolerable second-line or later therapy for pLGG. As familiarity with these targeted agents increases, their indications for use continue to expand and Phase 3 clinical trials investigating their utility in the front-line setting are ongoing. We have adopted mitigation strategies for their associated toxicities; skin toxicity, in particular, is now managed by prevention strategies and early dermatologic intervention. This review highlights current approaches for the clinical implementation of MEK and RAF kinase inhibitors for pLGG, focusing on the practical aspects of drug administration, toxicity management, response monitoring, and distribution to patients experiencing geographic or financial barriers to care. Additionally, we review important considerations for the off-label use of these agents while contemporaneous clinical trials assessing front-line efficacy are ongoing. We discuss the potential for more expansive or histology-agnostic tumor targeting using MEK inhibitors, harnessing their biologic relevance for other\n                    <jats:italic>RAS<\/jats:italic>\n                    -altered conditions.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2025.1520316","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T02:03:52Z","timestamp":1739239432000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Integrating MAPK pathway inhibition into standard-of-care therapy for pediatric low-grade glioma"],"prefix":"10.3389","volume":"15","author":[{"given":"Erin E.","family":"Crotty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee A.","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"Abdelbaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noad149","article-title":"CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020","volume":"25","author":"Ostrom","year":"2023","journal-title":"Neuro Oncol"},{"key":"B2","doi-asserted-by":"publisher","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":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noae008","article-title":"A paradigm shift in how we treat pediatric low-grade glioma\u2014Targeting the molecular drivers","volume":"26","author":"Ziegler","year":"2024","journal-title":"Neuro-Oncology"},{"key":"B4","article-title":"Intracranial visual pathway gliomas in children with neurofibromatosis","volume":"1","author":"Packer","year":"1988","journal-title":"Neurofibromatosis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(89)80137-4","article-title":"Optic gliomas in children with neurofibromatosis type 1","volume":"114","author":"Listernick","year":"1989","journal-title":"J Pediatr"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa036","article-title":"Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference","volume":"22","author":"Packer","year":"2020","journal-title":"Neuro-Oncology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2022.884250","article-title":"Neurosurgery for optic pathway glioma: optimizing multidisciplinary management","volume":"9","author":"Samples","year":"2022","journal-title":"Front Surgery"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-031-62017-1_9","volume-title":"Low-Grade Glioma in Children and Adolescents","author":"Zapotocky","year":"2024"},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.68.1585","article-title":"Phase II weekly vinblastine for chemotherapy-na\u00efve children with progressive low-grade glioma: A canadian pediatric brain tumor consortium study","volume":"34","author":"Lassaletta","year":"2016","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.04.019","article-title":"A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (\u226416 years) low grade glioma - 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