The alpha isoform of PI3K (PI3Kα) is one of the most frequently mutated kinases in solid tumors. Structural insights from the study of normal and mutated forms of PI3Kα suggest a release of inhibition by its regulating subunit p85 as well as altered membrane binding as causes for the observed biochemical over activity of the mutants. The mutational activation of PI3Kα permits cell survival in culture when growth factors are limiting. PI3Kα is a heterodimer of a catalytic subunit encoded by PIK3CA and one of several regulatory subunits. The high frequency of PIK3CA mutations in human tumors, the localization of mutations to particular "hotspot" regions, and the enhanced enzymatic activity of the mutant gene's products have made PI3Kα a preferred target for drug development. Indeed, PI3KCA is one of the two most highly mutated oncogenes ever discovered (the other being KRAS). For these reasons, many academic and industrial groups are attempting to develop inhibitors of this enzyme.
Schmidt-Kittler O, Zhu J, Yang J, et al. PI3Kα Inhibitors That Inhibit Metastasis. Oncotarget. 2010;1(5):339-348.