Peter K. Vogt

PI3K signaling shows gain of function in numerous and diverse human cancers. The gene coding for the catalytic subunit p110α of class IA PI3K frequently carries point mutations that map to one of three “hot spots” in the gene. p110α proteins carrying one of these mutations show increased lipid kinase activity compared to wild type p110α. The mutants also strongly stimulate Akt signaling and are oncogenic in cell culture and in the animal. The mutated p110α proteins are ideal targets for small molecule inhibitors; they are cancer specific, they are enzymes, and they show gain of function.