One of these adaptive mechanisms is stimulation of C-peptide and insulin secretion, which activates insulin receptors in tumors, further limiting the suppression of PI3K.9 Second, therapeutic inhibition with pan-PI3K and PI3K inhibitors is associated with toxicities, such as hyperglycemia, rash, and gastrointestinal side effects as a result of inhibition of wild type PI3K isozymes, hence also preventing sustained and specific inhibition of mutant PIK3CA. Here, PIK3CA is linked to Hyperglycemia.