Radiotherapy and radio-sensitization in H3K27M-mutated diffuse midline gliomas |
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| Authors: | Chao Liu Shuwen Kuang Lei Wu Quan Cheng Xuan Gong Jun Wu Longbo Zhang |
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| Institution: | 1. Departments of Oncology, Xiangya Hospital, Central South University, Changsha, China;2. Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China;3. Departments of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China |
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| Abstract: | Background H3K27M 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 H3K27M DMGs; however, the radio-resistance is commonly observed. Methods We summarized current understandings of the molecular responses of H3K27M DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement. Results 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. Conclusions The advances in mechanisms of radio-resistance in H3K27M DMGs promote the potential targets to enhance the sensitivity to radiotherapy. |
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| Keywords: | cell checkpoints DMG DNA damage and repair H3K27M radio-sensitization |
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