Cell cycle analysis, apoptosis assays, lactate dehydrogenase (LDH) release measurements, Western blotting, and xenograft tumor models were employed to explore the synergistic regulation of IGF1R by HIF1α and HIF2α, focusing on activation of the PI3K/AKT signaling pathway and its contribution to GBM drug resistance. Here, EPAS1 is linked to glioblastoma.