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Pediatric high-grade glioma: moving toward subtype-specific multimodal therapy
Hannah V Chatwin1, Joselyn Cruz Cruz1, Adam L Green1,2
1Department of Pediatrics, Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Aurora, CO, USA.
Abstract:
Pediatric high-grade gliomas (pHGG) comprise a deadly, heterogenous category of pediatric gliomas with a clear need for more effective treatment options. Advances in high-throughput molecular techniques have enhanced molecular understanding of these tumors, but outcomes are still poor, and treatments beyond resection and radiation have not yet been clearly established as standard of care. In this review, we first discuss the history of treatment approaches to pHGG to this point. We then review four distinct categories of pHGG, including histone 3-mutant, IDH-mutant, histone 3/IDH-wildtype, and radiation-induced pHGG. We discuss the molecular understanding of each subgroup and targeted treatment options in development. Finally, we look at the development and current status of two novel approaches to pHGG as a whole: localized convection-enhanced chemotherapy delivery and immunotherapy, including checkpoint inhibitors, vaccine therapy, and CAR-T cells. Through this review, we demonstrate the potential for rational, molecularly driven, subtype-specific therapy to be used with other novel approaches in combinations that could meaningfully improve the prognosis in pHGG.
Insights
Pediatric high-grade gliomas (pHGG) require better treatments. Molecularly targeted therapies and novel approaches like immunotherapy offer promising new avenues for improving outcomes in these aggressive brain tumors.
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.
