Wierzbicki Kyle, Ravi Karthik, Franson Andrea, Bruzek Amy, Cantor Evan, Harris Micah, Homan Morgan J, Marini Bernard L, Kawakibi Abed Rahman, Ravindran Ramya, Teodoro Rodrigo, Yadav Viveka Nand, Koschmann Carl
University of Michigan Medical School, 3520D MSRB I 1150 W Medical Center Dr., Ann Arbor, MI, 48109, USA.
Department of Neurosurgery, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
Curr Oncol Rep. 2020 Feb 6;22(2):19. doi: 10.1007/s11912-020-0877-0.
H3K27M is a frequent histone mutation within diffuse midline gliomas and is associated with a dismal prognosis, so much so that the 2016 CNS WHO classification system created a specific category of "Diffuse Midline Glioma, H3K27M-mutant". Here we outline the latest pre-clinical data and ongoing current clinical trials that target H3K27M, as well as explore diagnosis and treatment monitoring by serial liquid biopsy.
Multiple epigenetic compounds have demonstrated efficacy and on-target effects in pre-clinical models. The imipridone ONC201 and the IDO1 inhibitor indoximod have demonstrated early clinical activity against H3K27M-mutant gliomas. Liquid biopsy of cerebrospinal fluid has shown promise for clinical use in H3K27M-mutant tumors for diagnosis and monitoring treatment response. While H3K27M has elicited a widespread platform of pre-clinical therapies with promise, much progress still needs to be made to improve outcomes for diffuse midline glioma patients. We present current treatment and monitoring techniques as well as novel approaches in identifying and targeting H3K27M-mutant gliomas.
H3K27M是弥漫性中线胶质瘤中常见的组蛋白突变，与预后不良相关，以至于2016年世界卫生组织中枢神经系统分类系统创建了“弥漫性中线胶质瘤，H3K27M突变型”这一特定类别。在此，我们概述了针对H3K27M的最新临床前数据和正在进行的临床试验，以及通过系列液体活检进行诊断和治疗监测的情况。
多种表观遗传化合物在临床前模型中已显示出疗效和靶向作用。咪哒酮ONC201和吲哚胺2,3-双加氧酶1（IDO1）抑制剂吲哚莫德已显示出针对H3K27M突变型胶质瘤的早期临床活性。脑脊液液体活检在H3K27M突变型肿瘤的诊断和监测治疗反应方面已显示出临床应用前景。虽然H3K27M引发了一个有前景的广泛临床前治疗平台，但仍需取得很大进展以改善弥漫性中线胶质瘤患者的预后。我们介绍了当前的治疗和监测技术以及识别和靶向H3K27M突变型胶质瘤的新方法。
