The tumor suppressor function of the 3-phosphoinositide phosphatase PTEN [20,21], the frequent somatic mutation of phosphatidylinositol (PI) 3-kinase in human cancers [23], and the discovery of a germline Akt2 loss-of-function mutation in a family with autosomal dominant insulin-resistant diabetes [58] underscore the central role of this pathway in human disease. This evidence concerns the gene PTEN and cancer.