The tumor heterogeneity, dynamic variation and crosstalk of numerous cell death-related signaling pathways, such as phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT), mitogen activated protein kinases (MAPK)/extracellular regulated protein kinases (ERK), and inhibitor of NF-κB (IκB)/nuclear factor-kappa B (NF-κB), may be associated with the resistance of targeted therapy. The gene discussed is AKT1; the disease is neoplasm.