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Targeted Therapies for Pediatric Central Nervous System Tumors

  • Nicholas Shawn Whipple
  • Amar Gajjar
Chapter

Abstract

Recent discoveries have significantly enhanced our understanding of the biology of pediatric central nervous system tumors. Molecularly defined targeted therapies are now being used to treat subgroups of these tumors, mostly in the setting of clinical trials. These therapies include targeted inhibition of smoothened to treat sonic hedgehog medulloblastoma; of mammalian target of rapamycin to treat subependymal giant cell astrocytoma; and of the mitogen-activated protein kinase pathway to treat BRAF V600E-mutated low-grade and high-grade gliomas, KIAA1549:BRAF fusion-positive pilocytic astrocytoma, and plexiform neurofibroma. For many patients, the use of these targeted therapies has resulted in significant regression and/or improved control of their tumors, including tumors that are recurrent or refractory to conventional therapy.

Keywords

BRAF inhibitor (dabrafenib, vemurafenib) High-grade glioma Low-grade glioma MEK inhibitor (selumetinib, trametinib) mTOR inhibitor (everolimus) Plexiform neurofibroma Smoothened inhibitor (sonidegib, vismodegib) Sonic hedgehog medulloblastoma Subependymal giant cell astrocytoma 

Abbreviations

CNS

Central nervous system

HGG

High-grade glioma

LGG

Low-grade glioma

MAPK

Mitogen-activated protein kinase

MEK

Mitogen-activated extracellular signal-regulated kinase

mTOR

Mammalian target of rapamycin

NF1

Neurofibromatosis type 1

PN

Plexiform neurofibroma

PTCH1

Patched 1

SEGA

Subependymal giant cell astrocytoma

SHH

Sonic hedgehog

SMO

Smoothened

SUFU

Suppressor of fused

TSC

Tuberous sclerosis complex

WHO

World Health Organization

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Hematology/Oncology, Department of PediatricsUniversity of Utah and Primary Children’s HospitalSalt Lake CityUSA
  2. 2.Department of OncologySt. Jude Children’s Research HospitalMemphisUSA

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