AKT1 and breast cancer: Recombinant human rhIGFBP-3 was shown to potentiate the effect of Herceptin on Herceptin-resistant human breast cancer cells in vitro as well as in a xenograft model in vivo by reducing Akt and ERK signaling [66] and an exogenously administered protease-resistant IGFBP-2 was shown to inhibit the growth of breast cancer cells in vitro and in a xenograft model in vivo [67].