While temozolomide, the alkylating agent currently used in standard treatment for glioblastoma, has been shown to interconvert non-GCSs to GCSs thereby inducing a more aggressive phenotype and enhancing chemoresistance38, focusing new therapeutic approaches on impairing HIF-1α-mediated adaptation to hypoxia may be critical to disrupting the tumor microenvironment and overcoming the most aggressive features of glioma, particularly recurrence and chemoresistance14,39,40. This evidence concerns the gene HIF1A and glioma.