PI3K-Akt-mTOR signaling pathway (PI3K/AKT/mTOR pathway)

The PI3K-Akt-mTOR signaling pathway is a conserved intracellular network critical for regulating cell survival, growth, metabolism, and proliferation in response to environmental signals. It begins with the activation of phosphoinositide 3-kinase (PI3K), leading to membrane recruitment and activation of protein kinase B (Akt), which in turn activates the mechanistic target of rapamycin (mTOR)[1][3][4][7][9][10]. Abnormal activity or mutations within this pathway are common in cancers and some metabolic and developmental diseases, where they promote tumor growth, metastasis, angiogenesis, and treatment resistance. Because of its central role in cell survival and proliferation, the pathway, or its individual components (PI3K, Akt, mTOR), are frequently targeted by kinase inhibitors approved for cancer therapy[2][5][8]. However, as this is a pathway—not a single protein—the term is not a canonical name for a drug target and usually refers to the collection of the three main enzymes within it, with drugs most often designed to selectively inhibit one or more nodes (PI3K isoforms, Akt, or mTOR complexes).

Other names

PI3K/AKT pathwayPI3K/Akt/mTOR pathwayPI3K/Akt pathwayPhosphoinositide 3-kinase/Protein kinase B/Mechanistic target of rapamycin pathway

Inhibition of PI3K catalytic activity (blocks production of PIP3, preventing activation of Akt); Allosteric or ATP-competitive inhibition of mTOR kinase activity (suppresses cell growth, proliferation); Inhibition of Akt kinase activity (blocks phosphorylation of downstream effectors, induces apoptosis).