Phosphoinositide 3-kinase–AKT–mammalian target of rapamycin pathway (PI3K–AKT–mTOR pathway)

The Phosphoinositide 3-kinase–AKT–mammalian target of rapamycin pathway is a highly conserved, intracellular signal transduction cascade regulating cell metabolism, growth, proliferation, survival, motility, angiogenesis, and differentiation. The pathway begins with activation of PI3K by extracellular stimuli (such as growth factors binding to cell membrane receptors), followed by activation of AKT (protein kinase B), leading to phosphorylation of multiple downstream substrates—including mTOR (mechanistic/mammalian target of rapamycin)—that regulate protein synthesis, cell growth, and survival. Dysregulation or mutation of components in this pathway is a hallmark of many cancers and other diseases, making it an attractive therapeutic target for kinase inhibitors, mTOR inhibitors, and combination therapies. However, its central role in normal cellular functions introduces significant safety and resistance challenges in clinical development and application.

Other names

PI3K–AKT pathwayPI3K–AKT–mTOR signaling pathwayPI3K–AKT signaling pathwayPhosphatidylinositol 3-kinase/Protein kinase B pathwayPI3K/PKB/mTOR pathway

Inhibition of kinase activity (PI3K, AKT, or mTOR) to block pathway signaling. Induction of apoptosis and inhibition of cell proliferation by blocking downstream survival signals. Suppression of metabolic and protein synthesis pathways via mTOR inhibition.