While the negative response to MK2206-HCl was unexpected considering our previous findings on the role of phospho-AKT signaling in EDB-FN regulation 45 in breast cancer cells, we speculate that the enhanced plasticity and overexpression of the drug efflux pump MDR-1 could have rendered the DLD1-DR tumors non-responsive to MK2206-HCl. The gene discussed is ABCB1; the disease is breast carcinoma.