Therefore, inhibiting the protective metabolic and autophagic responses under hypoxia, via the activation of proteasomal degradation of HIF1A/2A through the inhibition of HIF1A/2A-associated USPs and/or SIAH1/2, or by HIF1A/2A-targeting PROTACs, may be a promising avenue for sensitizing GBM cells to the existing and future therapies. Here, HIF1A is linked to glioblastoma.