Mutation of the PIK3CA oncogene in human cancers

Abstract

It is now well established that cancer is a genetic disease and that somatic mutations of oncogenes and tumour suppressor genes are the initiators of the carcinogenic process. The phosphatidylinositol 3-kinase signalling pathway has previously been implicated in tumorigenesis, and evidence over the past year suggests a pivotal role for the phosphatidylinositol 3-kinase catalytic subunit, PIK3CA, in human cancers. In this review, we analyse recent reports describing PIK3CA mutations in a variety of human malignancies, and discuss their possible implications for diagnosis and therapy.

Figure 1

(A) The main reaction catalysed by PI3K: phosphatidylinositol (PI) 4,5 bisphosphate (PIP₂) to phosphatidylinositol (PI) 3,4,5-triphosphate (PIP₃). (B) PI3K is activated upon ligand binding to a receptor tyrosine kinase (RTK), which then activates the regulatory subunit (p85) to bind the catalytic p110α subunit. This ultimately triggers various downstream signalling cascades resulting in cell survival, apoptosis, transformation, metastasis, and cell migration. (C) Schematic representation of PIK3CA (p110α catalytic subunit of PI3K) and its functional domains with the most common somatic mutations, E542K, E545K and H1047R within the helical and kinase domains indicated.