Due to the interaction of several signaling pathways that lead to “out of control” of GBM, including EGFR, PIK3CA, PDGF, and NF-κB, inhibition of at least one of these pathways is likely to lead to reactivity upregulation of other pathways (Pan et al., 2021), which may be largely responsible for the historical failure of targeted therapies. Here, PIK3CA is linked to glioblastoma.