PI3Kα

PI3Kα (p110α), encoded by PIK3CA, is a class IA phosphoinositide 3-kinase catalytic subunit that forms a heterodimer with p85 regulatory proteins and catalyzes the phosphorylation of phosphatidylinositol-(4,5)-bisphosphate to generate phosphatidylinositol-(3,4,5)-trisphosphate, thereby regulating cell growth, proliferation, survival, migration, and metabolic signaling^[1][2]. Mechanistically, PI3Kα is a central component of the PI3K-AKT-mTOR signaling axis and functions downstream of receptor tyrosine kinases and RAS proteins to amplify intracellular growth and survival pathways^[3][4]. Dysregulation of this pathway is among the most common molecular events in human cancer, and activating mutations in PIK3CA promote tumor initiation, progression, and therapeutic resistance through sustained PI3K signaling^[3][5]. In disease models, disruption of the RAS-PI3Kα interaction suppresses tumor growth and angiogenesis, highlighting the importance of PI3Kα-dependent signaling in oncogenic processes^[4]. Compared with related class I PI3K isoforms, p110α and p110β are broadly expressed across tissues, whereas p110δ is predominantly expressed in leukocytes, indicating distinct physiological functions and therapeutic opportunities among isoforms^[6]. Furthermore, PTEN-deficient tumors frequently depend on p110β activity, emphasizing a biologically important distinction between PI3Kα- and PI3Kβ-driven signaling networks^[2]. For experimental and translational applications, isoform-selective PI3Kα inhibitors, including alpelisib, have been developed to target PIK3CA-driven malignancies, making PI3Kα a major focus of precision oncology research^[5].