These disappointing results can be partly explained by the redundancy of upstream signaling mechanisms that result in PI3K/Akt activation (e.g., EGFR, c-MET, and PDGFR), as well as by some intracellular mediators acting downstream of PI3K/AKT that prevent successful cytotoxic activity, or simply due to tumor heterogeneity. The gene discussed is AKT1; the disease is neoplasm.