Phosphoinositide 3-kinase inhibition in cancer treatment

Over the past ten years, our knowledge of the integral role that the phosph oinositide 3-kinases (P13Ks) and their 3 ' -phosphorylated lipid products ( 3 ' -phosphorylated phosphoinositides; 3P-PIs) play in the mediation of sig nal transduction, cytoskeletal rearrangements and membrane trafficking has expanded considerably. They are now known to be involved in the regulation of cell growth, differentiation, mobility, proliferation and survival and h ence they have become a potential target for the control of the growth and spread of cancer cells. More recently, the correlation of the multiplicity of isomers (both catalytic and regulatory) within the different classes of the P13Ks with their functional relevance has become possible. This, combin ed with our further understanding of the protein recognition patterns for t heir different 3P-PIs and the newly-described pathways in the control of th e levels of these by dephosphorylation, has provided new aspects and areas for interference in these multiple P13K signalling pathways. However, in th e search for effective, non-toxic, drugs for use in the treatment of cancer s, these individual targets for P13K inhibition need to be further correlat ed with the specific in vivo effects on cell survival, invasivity and metas tatic potential. Here, the range of P13K inhibition targets are discussed i n the light of recent experimental findings, with a view to the exploitatio n of their specificities in new approaches to effective cancer treatments b ased on P13K activity inhibition.