Aberrant hedgehog pathway activity and mTORC2 upregulation are always associated with high-grade GBM formation.14, 15 TCGA-GBM database analysis suggests a strong correlation between Gli1, Gli2, Gli3 and Ptch1 mRNA expression and hedgehog pathway activity in GBM formation.16 In a Drosophila model, loss of functional Rictor and SIN1 alleles prevented glioma formation, demonstrating requirement of mTORC2.17 Cumulatively, all these correlation patterns are suggestive of the necessity of both the canonical Hh pathway and mTORC2 activities in GBM. This evidence concerns the gene GLI3 and central nervous system cancer.