Finally, the adverse effect profile and toxicities of PI3K inhibitors, most notably by inhibition of insulin signaling resulting in high-grade hyperglycemia, have previously been described to be dose and treatment-limiting.18-20 Complete inhibition of the pathway may be possible with improved therapeutic effect if on-target toxicities can be managed or optimized.34 Optimal patient selection by biomarkers may thus allow for lower therapeutic doses and improved toxicity profile, overall improving the efficacy of PI3K inhibitors. The gene discussed is INS; the disease is Hyperglycemia.