Background: A substantial number of epidemiologic and experimental studies support an important role for Class I phosphatidylinositol 3-kinases (PI3Ks) in the biology of human cancer.
Objective: This article reviews the authors' understanding of the role of Class IA PI3K in the biology of human cancers and present discovery efforts to identify and develop inhibitors of this class of lipid kinases.
Methods: Books, journals, databases and websites have been searched to find the latest information on the subject.
Results/conclusions: In spite of the progress made over the past few years, more studies are still needed to better understand the biology of this pathway, its interaction(s) with other signaling cascades, and the role of the individual paralogs and PI3Kalpha mutants in human cancer. From a drug discovery perspective, medicinal chemistry efforts have led to the discovery of new pan-PI3K and isoform selective inhibitors with improved specificity, potency and pharmaceutical properties. Phase I clinical studies have been initiated with some of these PI3K inhibitors and the efficacy and therapeutic index of this new generation of anticancer agents is eagerly awaited.