Our knowledge on the role of the different
lipid messengers produced by
phosphoinositide 3-kinases (PI3Ks) in normal and
cancer cells as well as in platelets during arterial
thrombosis has greatly expanded these last 15 years. PI3Ks are a family of
lipid kinases that catalyze the phosphorylation of the D3 position of the
inositol ring of
phosphoinositides to produce
phosphatidylinositol 3-phosphate (
PtdIns3P),
phosphatidylinositol 3,4-bisphosphate (
PtdIns(3,4)P2), and phosphatidylinositol-3,4,5 trisphosphate (
PtdIns(3,4,5)P3). These D3-phosphoinositides act as intracellular messengers recruiting effector
proteins involved in the control of diverse cellular functions including survival, proliferation, migration, membrane trafficking, and cytoskeleton dynamics. The current idea is that the different
isoforms of PI3Ks produce specific pools of
lipids that regulate in time and space, at the membrane/cytosol interface, the formation of appropriate functional
protein complexes. Dysregulation of PI3K-dependent pathways is directly involved in the etiology of several pathologies including
cancers where the PI3K/AKT/
mTORC1 axis is frequently aberrantly activated. Moreover,
PtdIns(3,4,5)P3 production has been shown to play an essential role in platelet functions, particularly in the formation of a stable platelet
thrombus at high shear rate. Therefore, PI3Ks are attractive therapeutic targets in the treatment of
cancer and arterial
thrombosis. In this review, we will discuss the role of the different
lipid products of PI3K
isoforms in the context of
cancer and
thrombosis and the development of selective PI3Ks inhibitors in the treatment of these diseases.