Recent Advances in Targeted Therapies for Adult Gliomas

Price M, Ballard C, Benedetti J, Neff C, Cioffi G, Waite KA, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united States in 2017–2021. Neuro Oncol. 2024;26:vi1–85. https://doi.org/10.1093/neuonc/noae145.

Article  PubMed  PubMed Central  Google Scholar 

Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–73. https://doi.org/10.1056/NEJMoa0808710.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20. https://doi.org/10.1007/s00401-016-1545-1.

Article  PubMed  Google Scholar 

Bailey P, Cushing H. A Classification of the Tumors of the Glioma Group on a Histogenetic Basis with a Correlated Study of Prognosis. J. B. Lippincott Company; 1926.

Google Scholar 

Zülch KJ. Histological typing of tumours of the central nervous system. Geneva: World Health Organization; 1979.

Google Scholar 

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23:1231–51. https://doi.org/10.1093/neuonc/noab106.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Miller JJ, Gonzalez Castro LN, McBrayer S, Weller M, Cloughesy T, Portnow J, et al. Isocitrate dehydrogenase (IDH) mutant gliomas: a Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol. 2023;25:4–25. https://doi.org/10.1093/neuonc/noac207.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, et al. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer. 2020;122:1580–9. https://doi.org/10.1038/s41416-020-0814-x.

Article  PubMed  PubMed Central  Google Scholar 

Dewdney B, Jenkins MR, Best SA, Freytag S, Prasad K, Holst J, et al. From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress. Signal Transduct Target Ther. 2023;8:400. https://doi.org/10.1038/s41392-023-01637-8.

Article  PubMed  PubMed Central  Google Scholar 

Pouyan A, Ghorbanlo M, Eslami M, Jahanshahi M, Ziaei E, Salami A, et al. Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies. Mol Cancer. 2025;24:58. https://doi.org/10.1186/s12943-025-02267-0.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wen PY, Weller M, Lee EQ, Touat M, Khasraw M, Rahman R, et al. Glioblastoma in adults: A society for Neuro-Oncology (SNO) and European society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol. 2025;noaf177. https://doi.org/10.1093/neuonc/noaf177.

Nakhate V, Lasica AB, Wen PY. The role of mutant IDH inhibitors in the treatment of glioma. Curr Neurol Neurosci Rep. 2024;24:631–43. https://doi.org/10.1007/s11910-024-01378-3.

Article  CAS  PubMed  Google Scholar 

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. https://doi.org/10.1056/NEJMoa043330.

Article  CAS  PubMed  Google Scholar 

Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739–44. https://doi.org/10.1038/nature08617.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 2012;483:479–83. https://doi.org/10.1038/nature10866.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Duncan CG, Barwick BG, Jin G, Rago C, Kapoor-Vazirani P, Powell DR, et al. A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation. Genome Res. 2012;22:2339–55. https://doi.org/10.1101/gr.132738.111.

Article  CAS  PubMed  PubMed Central  Google Scholar 

DiNardo CD, Stein EM, Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378:2386–98. https://doi.org/10.1056/NEJMoa1716984.

Stein EM, Fathi AT, DiNardo CD, Pollyea DA, Roboz GJ, Collins R, et al. Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. Lancet Haematol. 2020;7:e309–19. https://doi.org/10.1016/S2352-3026(19)30284-4.

Article  PubMed  Google Scholar 

Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Final overall survival efficacy results of Ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021;7:1669–77. https://doi.org/10.1001/jamaoncol.2021.3836.

Article  PubMed  PubMed Central  Google Scholar 

Rudà R, Horbinski C, van den Bent M, Preusser M, Soffietti R. IDH inhibition in gliomas: from preclinical models to clinical trials. Nat Rev Neurol. 2024;20:395–407. https://doi.org/10.1038/s41582-024-00967-7.

Article  CAS  PubMed  Google Scholar 

Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, et al. Ivosidenib in isocitrate dehydrogenase 1–mutated advanced glioma. J Clin Oncol. 2020;38:3398–406. https://doi.org/10.1200/JCO.19.03327.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA, Maher EA, Janku F, et al. Vorasidenib, a dual inhibitor of mutant IDH1/2, in recurrent or progressive glioma; results of a first-in-human phase I trial. Clin Cancer Res. 2021;27:4491–9. https://doi.org/10.1158/1078-0432.CCR-21-0611.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Konteatis Z, Artin E, Nicolay B, Straley K, Padyana AK, Jin L, et al. Vorasidenib (AG-881): a first-in-class, brain-penetrant dual inhibitor of mutant IDH1 and 2 for treatment of glioma. ACS Med Chem Lett. 2020;11:101–7. https://doi.org/10.1021/acsmedchemlett.9b00509.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, et al. Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023;29:615–22. https://doi.org/10.1038/s41591-022-02141-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389:589–601. https://doi.org/10.1056/NEJMoa2304194.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wen P, Mellinghoff I, van den Bent M, Blumenthal D, Touat M, Peters K, et al. LTBK-06. Impact of vorasidenib treatment on mutant IDH1 or IDH2 diffuse glioma tumor growth rate: results from the randomized, double-blind, phase 3 Indigo study. Neuro Oncol. 2023;25:v310–1. https://doi.org/10.1093/neuonc/noad179.1202.

Article  PubMed Central  Google Scholar 

Mellinghoff IK, van den Bent MJ, Touat M, Blumenthal DT, Peters KB, Ellingson BM, et al. CTNI-53. A global, randomized, double-blinded, phase 3 study of vorasidenib versus placebo in patients with adult-type diffuse glioma with an IDH1/2 mutation (indigo): updated efficacy results. Neuro Oncol. 2024;26:viii108–9. https://doi.org/10.1093/neuonc/noae165.0420.

Article  PubMed Central  Google Scholar 

van den Bent MJ, French PJ, Brat D, Tonn JC, Touat M, Ellingson BM, et al. The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: how should they inform treatment decisions in the era of IDH inhibitors? Neuro Oncol. 2024;26:1805–22. https://doi.org/10.1093/neuonc/noae107.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Douw L, Klein M, Fagel SS, van den Heuvel J, Taphoorn MJ, Aaronson NK, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. La

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