Phosphoinositide 3-kinases as targets for therapeutic intervention.

Abstract

Phosphoinositide 3-kinases (PI3K) represent a family of intracellular signaling proteins, which control a variety of important cellular functions such as proliferation, apoptosis and migration. Recent findings suggest an involvement of PI3K in the pathogenesis of numerous diseases including cancer, heart failure and autoimmune/inflammatory disorders. This review summarizes the current knowledge of the emerging therapeutic value of PI3K as targets for the intervention of several pathological disorders and in particular focusing on oncogenesis. A brief introduction on the molecular and biochemical features of these signaling proteins will be followed by a depiction of signaling interactions of PI3K in a cellular context. PI3K dependent signaling involved in the control of cell growth, proliferation, survival and cytoskeletal remodeling and the link to cellular dysfunctions will be discussed. Further we will summarize the phenotypic consequences by genetic targeting PI3K signaling in mice. In its final part this review outlines challenges and activities considering PI3K as targets for therapeutic intervention and progress in the development of first generation small molecule inhibitors.