Phosphatidylinositol 3-kinase catalytic subunit alpha isoform (PI3K-alpha (p110α))

Phosphatidylinositol 3-kinase catalytic subunit alpha isoform (PI3K-alpha, p110α) is the catalytic component of class IA PI3K enzymes, produced by the PIK3CA gene. This lipid kinase phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to generate phosphatidylinositol-3,4,5-trisphosphate (PIP3), initiating intracellular signaling cascades crucial for cell growth, proliferation, survival, metabolism, and migration. PI3K-alpha activity is tightly regulated, and its dysregulation via activating mutations is strongly implicated in the pathogenesis of many cancers and metabolic diseases. Selective pharmaceutical inhibition of PI3K-alpha is an approved strategy in precision oncology, especially in cancers harboring activating PIK3CA mutations. Key challenges in targeting PI3K-alpha include metabolic toxicities and resistance mechanisms.

Other names

PI3K-alphap110-alphaphosphoinositide-3-kinase catalytic alpha polypeptidephosphatidylinositol 3-kinase, catalytic, 110-KD, alphaphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoformPK3CA_HUMANptdIns-3-kinase subunit p110-alphaserine/threonine protein kinase PIK3CA

Inhibition of PI3K-alpha reduces phosphorylation of signaling lipids (PIP2 to PIP3), thereby decreasing AKT activation, ultimately suppressing cell growth, survival, and metabolism, especially in cancers with PIK3CA mutations. Reduction of downstream mTOR signaling, glycolysis, and anabolic metabolism.