Saito Ryuta
Department of Neurosurgery, Nagoya University, Graduate School of Medicine.
No Shinkei Geka. 2022 Jan;50(1):29-38. doi: 10.11477/mf.1436204529.
Diffuse midline glioma(DMG), H3 K27M-mutant is an infiltrative midline high-grade glioma with predominantly astrocytic differentiation and a K27M mutation in either H3F3A or HIST1H3B/C. It is commonly located in the brain stem, thalamus, and spinal cord. DMG is predominant in children but can occur in adults. Brain stem disease, known as diffuse intrinsic pontine glioma(DIPG), is the representative: -80% harbor the H3 K27M mutation. Generally, the prognosis of DMG is poor: the 2-year survival rate is < 10%, despite intensive research and therapies. Consequently, radiation is the only treatment and there is no effective chemotherapeutic regimen. The recent findings concerning the genetic profiles of DMG shed light on precision medicine. Until today, approximately 250 clinical trials with molecular targeted therapy as a strategy have been conducted for different biological pathways in DMG. Unfortunately, none of them has shown significant efficacy for DMG. One of the problems in these clinical trials is insufficient knowledge of whether the used molecular targeted agents penetrate the blood-brain barrier. Continuous efforts to develop effective precision medicine against DMG should pave the way for overcoming DMG in the future.
弥漫性中线胶质瘤（DMG），H3 K27M突变型是一种浸润性中线高级别胶质瘤，主要为星形细胞分化，且H3F3A或HIST1H3B/C存在K27M突变。它通常位于脑干、丘脑和脊髓。DMG在儿童中占主导，但也可发生于成人。脑干疾病，即弥漫性内生性脑桥胶质瘤（DIPG），是其代表：80%的病例存在H3 K27M突变。一般来说，DMG的预后较差：尽管进行了深入研究和治疗，其2年生存率仍低于10%。因此，放疗是唯一的治疗方法，且没有有效的化疗方案。最近关于DMG基因谱的研究结果为精准医学提供了线索。截至目前，已经针对DMG的不同生物学途径开展了约250项以分子靶向治疗为策略的临床试验。不幸的是，这些试验均未显示出对DMG有显著疗效。这些临床试验中的一个问题是，对于所使用的分子靶向药物是否能穿透血脑屏障了解不足。持续努力开发针对DMG的有效精准医学方法应能为未来攻克DMG铺平道路。
