Radiotherapy and radio-sensitization in H3K27M-mutated diffuse midline gliomas

BackgroundH3(K27M) mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer-related deaths in pediatric brain tumors with 5-year survival H3(K27M) DMGs; however, the radio-resistance is commonly observed. MethodsWe summarized current understandings of the molecular responses of H3(K27M) DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement. ResultsIonizing 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. ConclusionsThe advances in mechanisms of radio-resistance in H3(K27M) DMGs promote the potential targets to enhance the sensitivity to radiotherapy.

Automated summary

H3(K27M) mutated diffuse midline gliomas (DMGs) are highly aggressive and major cause of cancer-related deaths in pediatric brain tumors, with common radio-resistance. This study summarized current understandings of the molecular responses of H3(K27M) DMGs to radiotherapy and provided crucial insights into current advances in radiosensitivity enhancement.