Targeting lipid signalling in cancer

Phosphoinositide 3-kinases (PI3Ks) play an important role in a variety of cellular activities, including mitogenic signalling and cell survival, cytoskeletal remodelling, metabolic control, proliferation and vesicular trafficking. Consistent with their function in cell survival and growth, the gene for the class Iα PI3K catalytic subunit is a common site of cancer mutations. Ongoing structural studies of these enzymes and the complexes they make with their regulatory subunits have helped to clarify the mechanistic basis of this role in tumor development. The broad spectrum of biological activities associated with various isotypes of class I PI3Ks has led to an intense search for isotype-specific inhibitors as tools in mammalian cell biology and for therapeutic application.