Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas

Henriette Pedersen, Kjeld Schmiegelow, Petra Hamerlik

Abstract

Malignant gliomas (MG) are among the most prevalent and lethal primary intrinsic brain tumors. Although radiotherapy (RT) is the most effective nonsurgical therapy, recurrence is universal. Dysregulated DNA damage response pathway (DDR) signaling, rampant genomic instability, and radio-resistance are among the hallmarks of MGs, with current therapies only offering palliation. A subgroup of pediatric high-grade gliomas (pHGG) is characterized by H3K27M mutation, which drives global loss of di- and trimethylation of histone H3K27. Here, we review the most recent literature and discuss the key studies dissecting the molecular biology of H3K27M-mutated gliomas in children. We speculate that the aberrant activation and/or deactivation of some of the key components of DDR may be synthetically lethal to H3K27M mutation and thus can open novel avenues for effective therapeutic interventions for patients suffering from this deadly disease.

OriginalsprogEngelsk
TidsskriftCancers
Vol/bind12
Udgave nummer10
ISSN2072-6694
DOI
StatusUdgivet - 30 sep. 2020

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