Their strategy included targeting the PI3K/mTOR pathway with paxalisib, mitigating paxalisib-associated toxicity (particularly hyperglycemia) with the antidiabetic drug metformin, and tackling one potential resistance mechanism, namely upregulation of PKC signaling, with the PKC inhibitor enzastaurin (Figure 1) (2). This evidence concerns the gene PRRT2 and Hyperglycemia.