Multi-dimensional Integrative Profiling Identifies Novel Therapeutic Targets in Paediatric High-Grade Gliomas

High-grade gliomas (HGGs) are aggressive brain tumours in both adults and children, with survival rates below 20%. This study used advanced methods, including genetic CRISPR-Cas9 knock-out screens, “omics” datasets, and AI analytics, to uncover new treatment targets for childhood HGGs. The study identified that these tumours rely on the anti-apoptotic protein MCL1, and its dependency is linked to BCL2L1 gene methylation. The research also identified a mutation in the TMPRSS2 gene (V317M) linked to paediatric HGGs, with treatments targeting this mutation proving effective. These findings highlight MCL1 and mutant TMPRSS2 as promising therapeutic targets, offering hope for improved outcomes in children with these deadly tumours.