From man to mouse and back again: advances in defining tumor AKTivities in vivo

AKT hyperactivation is a common event in human cancers, and inhibition of oncogenic AKT activation is a major goal of drug discovery programs. Mouse tumor models that replicate AKT activation typical of human cancers provide a powerful means by which to investigate mechanisms of oncogenic signaling, identify potential therapeutic targets and determine treatment regimes with maximal therapeutic efficacy. This Perspective highlights recent advances using in vivo studies that reveal how AKT signaling supports tumor formation, cooperates with other mutations to promote tumor progression and facilitates tumor-cell dissemination, focusing on well-characterized prostate carcinoma mouse models that are highly sensitive to AKT activation. The implications of these findings on the therapeutic targeting of AKT and potential new drug targets are also explored.