PIK3CA and neoplasm: The rationale for using dual targeting inhibitors such as PI3K/mTORC1 or ATP-competitive mTORC1/mTORC2 inhibitors (Fig. 4) is that hyperactive PI3K/AKT/mTOR signaling is prevalent in a broad spectrum of human cancers; treatment of tumor cells with first generation rapalogs unexpectedly resulted in the upregulation of phosphorylated AKT and may potentially circumvent the effectiveness of targeting the pathway; and new evidence suggests that mTORC2, which is involved in the rephosphorylation of AKT, is also involved in cancer cell growth and survival [80].