title: Status of PI3K inhibition and biomarker development in cancer therapeutics.
abstract: The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Markman
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Atzori
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pérez-García
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: jbaselga@vhebron.net.
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D004791:Enzyme Inhibitors; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors