In terms of distinguishing treatment responses between high-grade and intermediate-grade CS, the multiplex assays demonstrated DOX inhibition of Insulin-R and p-Insulin-R in CDS11 but not CS1 cells, and increased relative levels of GSK-3b phosphorylation (silencing) in CS1 but not CDS11 cells, suggesting that the failure of DOX to inhibit insulin signaling in CS1 cells, combined with the suppression of GSK-3β activity, contributes to DOX chemotherapy resistance in CS1 cells. This evidence concerns the gene GSK3B and Cowden syndrome 1.