Phosphatidylinositol 3-kinase–Akt pathway (PI3K–Akt pathway)

The Phosphatidylinositol 3-kinase–Akt pathway (PI3K–Akt pathway) is a key intracellular signaling cascade that regulates diverse biological processes, including cell survival, proliferation, growth, metabolism, migration, and angiogenesis. It is activated by a variety of extracellular signals (e.g., growth factors) through receptor tyrosine kinases, which leads to activation of PI3K and subsequent generation of PIP3 at the plasma membrane. This recruits and enables activation of Akt (protein kinase B), a serine/threonine kinase, which then phosphorylates numerous downstream effectors to modulate cell fate. Dysregulation of this pathway is common in many human diseases, especially cancer, where mutations or loss of negative regulators (notably PTEN) or activating mutations in PI3K or Akt are frequent. The pathway is a major focus of drug development, with several PI3K and Akt inhibitors as approved or investigational therapies, but therapeutic targeting is challenged by pathway complexity, toxicity, and compensatory mechanisms[1][2][4][6][7][8].

Other names

PI3K/Akt pathwayPI3K–Akt signaling pathwayphosphoinositide 3-kinase–protein kinase B pathwayAkt signaling pathwayPI3K signaling pathway

Inhibition of kinase activity prevents downstream survival and proliferation signaling[2][6] Inhibition of the pathway at various levels leads to reduced tumor cell growth, induction of apoptosis, or decreased metabolism[2][6]