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Published on: December 28, 2017
Radiotherapy and radio-sensitization in H3K27M -mutated diffuse midline gliomas
Chao Liu1,2, Shuwen Kuang1, Lei Wu3
1Departments of Oncology, Xiangya Hospital, Central South University, Changsha, China.
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.
Insights
H3K27M mutated diffuse midline gliomas (DMGs) are aggressive pediatric brain tumors resistant to radiotherapy. Understanding molecular responses to radiation can reveal targets to improve treatment sensitivity.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Radiation Oncology
Background:
- H3K27M mutated diffuse midline gliomas (DMGs) are highly aggressive pediatric brain tumors with poor prognosis.
- Radiotherapy is the primary adjuvant treatment, but radio-resistance is a significant clinical challenge.
Purpose of the Study:
- To review the molecular mechanisms underlying radio-resistance in H3K27M DMGs.
- To highlight strategies for enhancing radiosensitivity in these tumors.
Main Methods:
- Literature review and synthesis of current research on H3K27M DMG response to radiotherapy.
- Analysis of molecular pathways involved in cell cycle checkpoints and DNA damage repair.
Main Results:
- Ionizing radiation (IR) induces DNA damage, but H3K27M DMGs exhibit disrupted cell cycle checkpoints and DNA damage repair (DDR) systems.
- Aberrant genetic/epigenetic changes, stemness, and epithelial-mesenchymal transition (EMT) contribute to radio-resistance by altering regulatory pathways.
Conclusions:
- Understanding the molecular basis of radio-resistance in H3K27M DMGs is crucial.
- Identifying and targeting these resistance mechanisms offers potential strategies to improve radiotherapy efficacy.
