Co-inhibition of the RAS–ERK pathway has shown promise against glioblastoma,15 DIPG,10 and other solid cancers.16,17 Crosstalk between the two pathways occurs at multiple points, including the ability of ERK and the downstream kinase ribosomal S6 protein kinase to compensate for AKT in the activation of mammalian target of rapamycin complex 1 (mTORC1) via inhibitory tuberous sclerosis complex 2 phosphorylation, MEK suppression of PI3K signaling by promoting membrane localization of phosphatase and tensin homolog, and AKT suppression of RAF via phosphorylation, as schematized in Figure 1. The gene discussed is AKT1; the disease is glioblastoma.