In HER2+ tumours, the MAPK/ERK pathway is activated through ERBB2, but PI3K/AKT pathway activation is additionally required, for example, via ERBB3 (HER3) upregulation (Fig. 8d), PIK3CA mutations or PTEN loss44, 45, 46, 47, 48, 49. This evidence concerns the gene PTEN and neoplasm.