title: Class IA phosphatidylinositol 3-kinase: from their biologic implication in human cancers to drug discovery.
abstract: 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.
  
  
  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.
authors.affiliation: Novartis Institutes for Biomedical Research (NIBR) Oncology, Novartis Pharma AG, Klybeckstrasse, WKL-125.1.08, CH-4002 Basel, Switzerland. sauveur-michel.maira@novartis.com
authors.forename: Sauveur-Michel
authors.initials: SM
authors.lastname: Maira
authors.forename: Charles
authors.initials: C
authors.lastname: Voliva
authors.forename: Carlos
authors.initials: C
authors.lastname: Garcia-Echeverria
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors
chemical_list: D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors