Pediatric high-grade glioma: moving toward subtype-specific multimodal therapy

Area of Science:

• Neuro-oncology
• Pediatric Oncology
• Molecular Pathology

Background:

• Pediatric high-grade gliomas (pHGG) are a deadly and diverse group of brain tumors with limited treatment options.
• Despite advances in molecular understanding, patient outcomes remain poor, with standard care primarily limited to surgery and radiation.

Purpose of the Study:

• To review historical and current treatment strategies for pHGG.
• To explore molecularly defined subgroups of pHGG and their associated targeted therapies.
• To examine novel therapeutic approaches, including convection-enhanced chemotherapy and immunotherapy.

Main Methods:

• Literature review of treatment history for pHGG.
• Analysis of molecular subgroups: histone 3-mutant, IDH-mutant, histone 3/IDH-wildtype, and radiation-induced pHGG.
• Review of emerging therapies: convection-enhanced chemotherapy, checkpoint inhibitors, vaccine therapy, and CAR-T cells.

Main Results:

• pHGG classification into distinct molecular subgroups aids in understanding tumor biology.
• Targeted therapies are under development for specific pHGG molecular subtypes.
• Convection-enhanced chemotherapy and various immunotherapies show potential for pHGG treatment.

Conclusions:

• Molecularly driven, subtype-specific therapies hold significant promise for pHGG.
• Combination strategies involving targeted agents and novel approaches may substantially improve prognosis.
• Further research into rational, combination-based treatments is crucial for advancing pHGG care.