Considering the activation of the PAM signaling network inGBM, Smith et al. designed a novel series of potent and selectiveclass-I PI3K inhibitors that demonstrated striking tumor growth inhibitorypotential against the U-87MG human GBM cell line (Figure 2).33 The group utilized a previously reported dual PI3K/mTOR inhibitor(1) as a chemical probe to understand the binding modeusing different isoforms of PI3K. This evidence concerns the gene PIK3CA and glioblastoma.