Abstract
Low grade gliomas are the most frequent brain tumors in children and encompass a spectrum of histologic entities which are currently assigned World Health Organisation grades I and II. They differ substantially from their adult counterparts in both their underlying genetic alterations and in the infrequency with which they transform to higher grade tumors. Nonetheless, children with low grade glioma are a therapeutic challenge due to the heterogeneity in their clinical behavior - in particular, those with incomplete surgical resection often suffer repeat progressions with resultant morbidity and, in some cases, mortality. The identification of up-regulation of the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway as a near universal feature of these tumors has led to the development of targeted therapeutics aimed at improving responses while mitigating patient morbidity. Here, we review how molecular information can help to further define the entities which fall under the umbrella of pediatric-type low-grade glioma. In doing so we discuss the specific molecular drivers of pediatric low grade glioma and how to effectively test for them, review the newest therapeutic agents and their utility in treating this disease, and propose a risk-based stratification system that considers both clinical and molecular parameters to aid clinicians in making treatment decisions.
Keywords:
Pediatric low-grade glioma; RAS/MAPK pathway; brain tumor; clinical trial; glioma; molecular diagnostics; neuro-oncology; neurofibromatosis type I; pediatric; risk stratification; targeted therapy.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Astrocytoma / diagnosis
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Astrocytoma / drug therapy
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Astrocytoma / genetics
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Astrocytoma / pathology
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Brain Neoplasms / diagnosis
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Brain Neoplasms / drug therapy
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Brain Neoplasms / genetics*
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Brain Neoplasms / pathology
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Child
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Ganglioglioma / diagnosis
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Ganglioglioma / drug therapy
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Ganglioglioma / genetics
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Ganglioglioma / pathology
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Glioma / diagnosis
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Glioma / drug therapy
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Glioma / genetics*
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Glioma / pathology
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High-Throughput Nucleotide Sequencing
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Humans
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Immunohistochemistry
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In Situ Hybridization, Fluorescence
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MAP Kinase Signaling System / genetics
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Membrane Proteins / genetics
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Molecular Diagnostic Techniques
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Molecular Targeted Therapy
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Neoplasm Grading
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Neoplasms, Neuroepithelial / diagnosis
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Neoplasms, Neuroepithelial / drug therapy
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Neoplasms, Neuroepithelial / genetics
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Neoplasms, Neuroepithelial / pathology
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Pathology, Molecular
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Polymerase Chain Reaction
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Polymorphism, Single Nucleotide
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors
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Proto-Oncogene Proteins B-raf / genetics
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Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors
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Receptor, Fibroblast Growth Factor, Type 1 / genetics
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Tuberous Sclerosis Complex 1 Protein / genetics
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Tuberous Sclerosis Complex 2 Protein / genetics
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Up-Regulation
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World Health Organization
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ras Proteins / genetics
Substances
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KIAA1549 protein, human
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Membrane Proteins
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Protein Kinase Inhibitors
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TSC1 protein, human
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TSC2 protein, human
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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FGFR1 protein, human
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Receptor, Fibroblast Growth Factor, Type 1
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinase Kinases
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ras Proteins