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

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.