Recent progess in phosphoinositide 3-kinases: oncogenic properties and prognostic and therapeutic implications.

Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that coordinate various fundamental cellular responses including mitogenic signaling, cell survival and proliferation, vesicular trafficking, cytoskeletal rearrangement and metabolism. Overexpression caused by genetic alterations such as the amplification or gain of copy numbers was frequently observed for various PI3Ks in different human cancers. In recent years, the high-frequency somatic mutations of PIK3CA observed in different human cancers further strengthen the notion that PI3Ks are optimal targets for therapeutic intervention. In this review, I summarize current experimental evidence about the transformation capability and oncogenic properties of different PIK3CA mutations identified in human cancers. I also discuss the association of PIK3CA mutations with other genetic markers, as well as the prognostic value of PIK3CA somatic mutations in human cancers. Finally, I discuss the application of PI3Ks as therapeutic targets in human cancers, including targeted and combinational therapies and the potential challenges that confront their clinical applications.