Phosphatidylinositol 3-kinase–phosphatase and tensin homolog–protein kinase B signaling pathway (PI3K/PTEN/Akt signaling pathway)

The PI3K/PTEN/Akt signaling pathway is a central regulator of cellular growth, survival, and metabolism, integrating signals from growth factor and hormone receptors at the cell membrane[1][4][5]. Upon activation, PI3K generates phosphatidylinositol-3,4,5-trisphosphate (PIP3), which recruits and activates Akt. Akt then phosphorylates many downstream targets, promoting cell survival, growth, and proliferation while inhibiting apoptosis[1][7]. PTEN acts as a critical negative regulator by dephosphorylating PIP3, thereby attenuating the pathway’s activity[4][5]. Dysregulation of this pathway—commonly through activating mutations of PIK3CA, loss of PTEN, or activating mutations in AKT—drives many human cancers, contributes to resistance to therapy, and is implicated in metabolic and neurodegenerative diseases. Because of this, each core component of the pathway—PI3K, Akt, mTOR, and PTEN—has been the focus of intensive drug development and clinical targeting[6].

Other names

PI3K-Akt pathwayAkt pathwayPI3K/AKT signaling pathwayPI3K/AKT/PTEN pathwayPI3K/AKT/mTOR signaling pathwayPI3K/Akt/mTOR/PTEN pathway

Inhibition of PI3K catalytic activity; Inhibition of AKT kinase activity; Inhibition of mTOR signaling; Restoration or enhancement of PTEN function (rare clinically, but a conceptual approach)[3][6]