Pediatric Gliomas: Molecular Landscape and Emerging Targets

Sophie M. Peeters; Yagmur Muftuoglu; Brian Na; David J. Daniels; Anthony C. Wang

doi:10.1016/j.nec.2020.12.001

Pediatric Gliomas: Molecular Landscape and Emerging Targets

Sophie M. Peeters, Yagmur Muftuoglu, Brian Na, David J. Daniels, Anthony C. Wang

Neurosurgery

Research output: Contribution to journal › Review article › peer-review

Abstract

Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.

Original language	English (US)
Pages (from-to)	181-190
Number of pages	10
Journal	Neurosurgery clinics of North America
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.nec.2020.12.001
State	Published - Apr 2021

Keywords

Diffuse midline glioma
Histone mutation
Molecular genetics
Next-generation sequencing
Pediatric glioma
Targeted therapy

ASJC Scopus subject areas

Surgery
Clinical Neurology

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10.1016/j.nec.2020.12.001

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title = "Pediatric Gliomas: Molecular Landscape and Emerging Targets",

abstract = "Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.",

keywords = "Diffuse midline glioma, Histone mutation, Molecular genetics, Next-generation sequencing, Pediatric glioma, Targeted therapy",

author = "Peeters, {Sophie M.} and Yagmur Muftuoglu and Brian Na and Daniels, {David J.} and Wang, {Anthony C.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2021",

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doi = "10.1016/j.nec.2020.12.001",

language = "English (US)",

volume = "32",

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T2 - Molecular Landscape and Emerging Targets

AU - Peeters, Sophie M.

AU - Muftuoglu, Yagmur

AU - Na, Brian

AU - Daniels, David J.

AU - Wang, Anthony C.

PY - 2021/4

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N2 - Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.

AB - Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.

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KW - Histone mutation

KW - Molecular genetics

KW - Next-generation sequencing

KW - Pediatric glioma

KW - Targeted therapy

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Pediatric Gliomas: Molecular Landscape and Emerging Targets

Abstract

Keywords

ASJC Scopus subject areas

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