びまん性橋膠腫（DIPG）に対する臨床試験の現状と展望

Current Status and Future Perspectives of Clinical Trials for Diffuse Intrinsic Pontine Gliomas（DIPG）

Point

・びまん性橋膠腫は依然として予後不良の疾患であるが，ヒストン変異の同定を契機に分子病態の理解が進み，分子異常やエピジェネティックな機序の解明が進展している．

・分子標的薬やキメラ抗原受容体T細胞療法をはじめとする免疫療法に加え，対流強化薬剤送達法や集束超音波などの新規薬剤送達法も試みられ，国際的に多くの臨床試験が展開されている．

・本邦においてはレジストリ研究が進みつつあり，今後の臨床試験基盤として新規治療開発の進展が期待される．

　Diffuse intrinsic pontine glioma (DIPG) remains one of the most devastating pediatric central nervous system tumors, with a median survival of approximately 11 months despite decades of research. The identification of histone H3 K27M mutations marked a pivotal moment, leading to major advancements in understanding the molecular and epigenetic characteristics of these tumors. This discovery enabled molecular classification and provided a basis for the development of novel therapeutic strategies. In recent years, clinical trials have investigated molecular targeted agents and epigenetic modulators. Immunotherapeutic approaches, such as CAR-T cell therapy, have shown promising early results, whereas innovative drug delivery techniques, including convection-enhanced delivery and focused ultrasound, aim to overcome the challenges of the blood-brain barrier. Two major international registries, the International DIPG/DMG Registry (IDIPGR) and the European Society for Paediatric Oncology (SIOPE) DIPG/DMG Registry, play crucial roles in collecting comprehensive clinical data across multiple countries. The DIPG-2023 registry study was launched in Japan to collect prospective clinical, radiological, and molecular data systematically and to provide a high-quality external control cohort for future intervention trials. These collaborative efforts highlight a new era of DIPG/DMG research, offering cautious optimism for therapeutic progress in this historically refractory disease.