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adults. Previously known as diffuse intrinsic pontine glioma (DIPG) or grade IV brain stem glioma, DMG has recently been reclassified as \u201cdiffuse midline glioma\u201d according to the WHO CNS5 nomenclature, expanding the DMG demographic. Limited therapeutic options result in a poor prognosis, despite advances in diagnosis and treatment. Radiotherapy has historically been the primary treatment modality to improve patient survival. Methods: This systematic literature review aims to comprehensively compile information on the diagnosis and treatment of DMG from 1 January 2012 to 31 July 2023. The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and utilized databases such as PubMed, Cochrane Library, and SciELO. Results: Currently, molecular classification of DMG plays an increasingly vital role in determining prognosis and treatment options. Emerging therapeutic avenues, including immunomodulatory agents, anti-GD2 CAR T-cell and anti-GD2 CAR-NK therapies, techniques to increase blood\u2013brain barrier permeability, isocitrate dehydrogenase inhibitors, oncolytic and peptide vaccines, are being explored based on the tumor\u2019s molecular composition. However, more clinical trials are required to establish solid guidelines for toxicity, dosage, and efficacy. Conclusions: The identification of the H3K27 genetic mutation has led to the reclassification of certain midline tumors, expanding the DMG demographic. The field of DMG research continues to evolve, with encouraging findings that underscore the importance of highly specific and tailored therapeutic strategies to achieve therapeutic success.<\/jats:p>","DOI":"10.3390\/jcm12165261","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:40:31Z","timestamp":1692009631000},"page":"5261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma"],"prefix":"10.3390","volume":"12","author":[{"given":"Gloria","family":"Miguel Llordes","sequence":"first","affiliation":[{"name":"Molecular Oncology Group, Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"},{"name":"Pediatric Cancer Center Barcelona, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-0615","authenticated-orcid":false,"given":"V\u00edctor Manuel","family":"Medina P\u00e9rez","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Curto Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Cruces, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-4552","authenticated-orcid":false,"given":"Irene","family":"Castells-Yus","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6618-2107","authenticated-orcid":false,"given":"Silvia","family":"V\u00e1zquez Sufuentes","sequence":"additional","affiliation":[{"name":"Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-1049","authenticated-orcid":false,"given":"Alberto J.","family":"Schuhmacher","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"},{"name":"Fundaci\u00f3n Aragonesa para la Investigaci\u00f3n y el Desarrollo (ARAID), 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Farrukh, S., Habib, S., Rafaqat, A., Sarfraz, Z., Sarfraz, A., Sarfraz, M., Robles-Velasco, K., Felix, M., and Cherrez-Ojeda, I. 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