Departments of Oncology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
CNS Neurosci Ther. 2023 Jul;29(7):1721-1737. doi: 10.1111/cns.14225. Epub 2023 May 8.
H3 mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer-related deaths in pediatric brain tumors with 5-year survival <1%. Radiotherapy is the only established adjuvant treatment of H3 DMGs; however, the radio-resistance is commonly observed.
We summarized current understandings of the molecular responses of H3 DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement.
Ionizing radiation (IR) can mainly inhibit tumor cell growth by inducing DNA damage regulated by the cell cycle checkpoints and DNA damage repair (DDR) system. In H3K27M DMGs, the aberrant genetic and epigenetic changes, stemness genotype, and epithelial-mesenchymal transition (EMT) disrupt the cell cycle checkpoints and DDR system by altering the associated regulatory signaling pathways, which leads to the development of radio-resistance.
The advances in mechanisms of radio-resistance in H3 DMGs promote the potential targets to enhance the sensitivity to radiotherapy.
H3 突变弥漫性中线脑胶质瘤（DMG）是极度侵袭性的肿瘤，也是儿童脑肿瘤相关死亡的主要原因，其 5 年生存率<1%。放疗是 H3 DMG 的唯一标准辅助治疗方法；然而，其通常存在放射抵抗。
我们总结了 H3 DMG 对放疗的分子反应，并对目前增强放射敏感性的进展提供了重要的见解。
电离辐射（IR）主要通过诱导细胞周期检查点和 DNA 损伤修复（DDR）系统调控的 DNA 损伤来抑制肿瘤细胞生长。在 H3K27M DMG 中，异常的遗传和表观遗传改变、干性基因型和上皮间质转化（EMT）通过改变相关的调节信号通路破坏了细胞周期检查点和 DDR 系统，导致放射抵抗的发展。
H3 突变弥漫性中线脑胶质瘤放射抵抗机制的研究进展促进了增强放疗敏感性的潜在靶点的发展。
