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New strategies in pediatric gliomas: molecular advances in pediatric low-grade gliomas as a model
Eric Raabe1, Mark W Kieran, Kenneth J Cohen
1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21287, USA.
Abstract:
Pediatric low-grade gliomas (pLGG) account for more brain tumors in children than any other histologic subtype. While surgery, chemotherapy and radiation remain the mainstay of upfront treatment, recent advances in molecular interrogation of pLGG have shown a small number of recurring genetic mutations in these tumors that might be exploited therapeutically. Notable findings include abnormalities in the RAS/MAP kinase pathway such as NF-1 loss or BRAF activation and mTOR activation. Recent identification of activating re-arrangements in c-MYB and MYBL1 in pediatric diffuse astrocytoma also provide candidates for therapeutic intervention. Targeting these molecularly identified pathways may allow for improved outcomes for patients as pediatric oncology moves into the era of biology-driven medicine.
Insights
Pediatric low-grade gliomas (pLGG) are common childhood brain tumors. Research identifies key genetic mutations, like RAS/MAP kinase and mTOR pathway alterations, offering new therapeutic targets for improved patient outcomes.
Area of Science:
- Pediatric oncology
- Neuro-oncology
- Molecular biology
Background:
- Pediatric low-grade gliomas (pLGG) represent the most common brain tumor subtype in children.
- Current treatments include surgery, chemotherapy, and radiation therapy.
- Limited understanding of pLGG molecular drivers has historically hindered targeted therapy development.
Purpose of the Study:
- To review recent advances in the molecular characterization of pediatric low-grade gliomas.
- To identify recurring genetic mutations and aberrant molecular pathways in pLGG.
- To explore the therapeutic potential of targeting these identified molecular alterations in pediatric brain tumors.
Main Methods:
- Review of current scientific literature on pediatric low-grade gliomas.
- Analysis of genetic mutation data from pediatric brain tumor studies.
- Identification of frequently altered signaling pathways, including RAS/MAP kinase, mTOR, c-MYB, and MYBL1.
Main Results:
- Recurring genetic abnormalities identified in pLGG include NF-1 loss, BRAF activation, and mTOR activation.
- Activating rearrangements in c-MYB and MYBL1 have been found in pediatric diffuse astrocytoma.
- These molecular alterations represent potential therapeutic targets.
Conclusions:
- Molecular interrogation of pLGG has revealed actionable targets.
- Targeting specific genetic mutations and pathways (e.g., RAS/MAPK, mTOR) holds promise for novel pediatric brain tumor treatments.
- The shift towards biology-driven medicine in pediatric oncology may improve treatment efficacy and patient outcomes.
