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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Neurotherapeutics 2017 ; 14 (2): 274-83 Nephropedia Template TP
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Targeting Epigenetic Pathways in the Treatment of Pediatric Diffuse (High Grade) Gliomas #MMPMID28233220
Vanan MI; Underhill DA; Eisenstat DD
Neurotherapeutics 2017[Apr]; 14 (2): 274-83 PMID28233220show ga
Progress in the treatment of adult high-grade gliomas (HGG), including chemoradiation with concurrent and adjuvant temozolomide for glioblastoma, has not translated into significant therapeutic advances for pediatric HGG, where overall survival has plateaued at 15% to 20%, especially when considering specialized pediatric treatment in tertiary care centers, maximal safe neurosurgical resection, optimized delivery of involved field radiation, and improvements in supportive care. However, recent advances in our understanding of pediatric HGG, including the application of next-generation sequencing and DNA methylation profiling, have identified mutations in the histone variant H3.3 and canonical H3.1 genes, respectively. These mutations are relatively specific to neuroanatomic compartments (cortex, midline structures, thalamus, brainstem) and are often associated with other mutations, especially in specific growth factor receptor tyrosine kinases. Targeting epigenetic pathways affected by these histone mutations, alone or in combination with small molecule inhibitors of growth factor receptor signaling pathways, will inform new treatment strategies for pediatric HGG and should be incorporated into novel cooperative group clinical trial designs.Electronic supplementary material: The online version of this article (doi:10.1007/s13311-017-0514-2) contains supplementary material, which is available to authorized users.