PIK3CA and Hyperglycemia: 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.