From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here
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PI3K – From the Bench to the Clinic and Back.- PI3K Book Introduction.- PDK1: The major transducer of PI 3-Kinase actions.- Protein Kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway.- Regulatory subunits of class IA PI3K.- The Regulation of Class IA PI 3-kinases by Inter-Subunit Interactions.- Phosphoinositide signalling pathways in metabolic regulation.- Role of RAS in the regulation of PI 3-kinase.- More than just kinases: The scaffolding function of PI3K.- PI3K signalling in neutrophils.- PI 3-kinase p110beta regulation of platelet integrin alpha IIbbeta3.- PI3Ks in lymphocyte signalling and development.- PI3 kinase regulation of skeletal muscle hypertrophy and atrophy.- Taking PI3Kdelta and PI3Kgamma one step ahead – Dual active PI3Kdelta/gamma inhibitors for the treatment of immune-mediated inflammatory diseases.- Oncogenic Mutations of PIK3CA in Human Cancers.- Structural Effects of Oncogenic PI3Kalpha Mutations.- Comparing the roles of the p110alpha and p110beta isoforms of PI3K in signaling and cancer.- Phosphatidylinositol 3-kinase (PI3K): The oncoprotein.- AKT Signaling in Physiology and Disease.- Faithfull modeling of PTEN loss driven diseases in the mouse.- PI3K as a target for therapy in haematological malignancies.- Clinical development of Phosphatidylinositol-3 kinase pathway inhibitors.- New inhibitors of the PI3K-Akt-m TOR pathway: Insights into m TOR signaling from a new generation of Tor kinase domain inhibitors (TORKinibs).- Small molecule inhibitors of the PI3-kinase family.- Targeting the RTK-PI3K-m TOR axis in malignant glioma: overcoming resistance.- Subject index.
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