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. Here, HIF1A is linked to neoplasm.