Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas
Brain Tumor Biology, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Juliane Maries Vej 8, DK-2100 Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, DK-2100 Copenhagen, Denmark
Author to whom correspondence should be addressed.
Received: 14 August 2020 / Revised: 27 September 2020 / Accepted: 28 September 2020 / Published: 30 September 2020
Approximately 50% of high-grade gliomas (HGG) in children are diffuse midline gliomas (DMGs), which carry the worst prognosis of all HGG, with a 2-year survival of less than 10%. DMGs are characterized by H3K27M mutation, rampant genomic instability, infiltrative growth, and radio-resistance. Recent large-scale profiling studies have identified some of the key molecular drivers underpinning DMG biology and therapeutic resistance. Here, we provide a comprehensive overview of studies that focus on DMG in the context of radio-resistance. We speculate that the aberrant activation of DNA damage response pathway (DDR) represents a druggable vulnerability, which could be leveraged to radio-sensitize DMGs.