The mechanism of beneficial anti-tumor activity for zotatifin combined with Ipatasertib (AKT inhibitor) was evaluated in the HER2 driven breast cancer SK-BR-3 model (Figures 4B, C, 5A), that had previously shown upregulation of HER3/p-HER3 upon treatment with an AKT inhibitor (20). This evidence concerns the gene AKT1 and breast cancer.