PIK3CA and cancer: (1) targeting different domains of the same protein with two drugs [for example, trastuzumab combined with pertuzumab for human epidermal growth factor receptor, HER2, in breast (10) and ovarian (11, 12) cancers]; horizontally targeting parallel signaling pathways [for example, combined MEK and PI3K/AKT inhibition (13, 14)], and vertically targeting up- and down-stream pathways in one SN [for example, targeting BRAF and MEK, HER2, and PI3K, PI3K/AKT and mTOR (15–17)].