Gliomas are the most common central nervous system (CNS) tumors in children and adolescents, and they display a particularly broad range of clinical behavior. The impact of CNS tumors on infant mortality is very important. During the last decades there have been no advances in the prognosis of these tumors, while therapeutic strategies have changed very little.
Pediatric high-grade glioma (pHGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis, with the most aggressive forms being lethal within months. Conventional treatments, such as chemotherapy and radiotherapy, have devastating effects on the developing brain of a child. Hence, novel treatment modalities are desperately needed. Dissecting the precise signaling pathways that lead to the tumor formation and identifying genetic vulnerabilities of the different pHGG subtypes will be instrumental to identify targeted therapeutic approaches.
Is it conceivable that suprantentorial versus infratentorial H3.3 K27M mutant gliomas arise from different cell of origin, with distinct neurodevelopmental signaling pathways. These pathways could represent specific genetic vulnerabilities that could be exploited from a therapeutic point of view.
