However, in HER-2 overexpressing breast cancer, PI3K signaling inhibition leads to increased HER-2-mediated ERK activation, pointing to yet another important growth-promoting signaling axis, the Ras-Raf-MEK-ERK pathway (Fig. 2), and the potential need for adding for instance MEK inhibitors in certain patient subgroups (Serra et al. 2011). This evidence concerns the gene ERBB2 and breast cancer.