Targeting inositol 1,4,5-trisphosphate receptor (IP<sub>3</sub>R)-mediated Ca<sup>2+</sup> signaling with 2-APB enhances the therapeutic efficacy of TMZ, suggesting that ITPR1-centered Ca<sup>2+</sup> signaling may represent a potential therapeutic vulnerability in aggressive GBM. This evidence concerns the gene ITPR1 and glioblastoma.