Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (PIK3CA)

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a key enzyme that encodes the p110α catalytic subunit of Class IA phosphoinositide 3-kinases (PI3Ks) [UniProt: P42336]. It functions as a critical transducer in the PI3K/AKT/mTOR signaling pathway, which is essential for regulating cell growth, proliferation, survival, and metabolism in response to growth factor stimulation [NCBI Gene: 5290]. Mutations in the PIK3CA gene, particularly "hotspot" mutations in the helical or kinase domains, are frequently observed in various human cancers, including breast, colorectal, and endometrial cancers, where they drive oncogenic transformation [PubMed: 25544881]. Additionally, somatic mutations in PIK3CA are linked to a group of overgrowth disorders known as PIK3CA-related overgrowth spectrum (PROS) [PubMed: 22729224]. Pharmacological targeting of PIK3CA with alpha-selective inhibitors like alpelisib has demonstrated clinical efficacy in treating PIK3CA-mutated, hormone receptor-positive advanced breast cancer [PubMed: 31091374]. However, because p110α is also involved in insulin signaling, therapeutic inhibition often results in metabolic side effects such as hyperglycemia [StatPearls: NBK557544].

Other names

p110-alphaPI3-kinase subunit alphaPI3K-alphaPhosphoinositide-3-kinase catalytic alpha polypeptidep110a

Selective inhibition of the p110α catalytic subunit of Class IA PI3K, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby inhibiting downstream AKT/mTOR signaling.