title: PI3K/AKT signaling pathway and cancer: an updated review.
abstract: Despite development of novel agents targeting oncogenic pathways, matching targeted therapies to the genetic status of individual tumors is proving to be a daunting task for clinicians. To improve the clinical efficacy and to reduce the toxic side effects of treatments, a deep characterization of genetic alterations in different tumors is required. The mutational profile often evidences a gain of function or hyperactivity of phosphoinositide 3-kinases (PI3Ks) in tumors. These enzymes are activated downstream tyrosine kinase receptors (RTKs) and/or G proteins coupled receptors (GPCRs) and, via AKT, are able to induce mammalian target of rapamycin (mTOR) stimulation. Here, we elucidate the impact of class I (p110α, β, γ, and δ) catalytic subunit mutations on AKT-mediated cellular processes that control crucial mechanisms in tumor development. Moreover, the interrelation of PI3K signaling with mTOR, ERK, and RAS pathways will be discussed, exploiting the potential benefits of PI3K signaling inhibitors in clinical use.
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin , Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Martini
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: De Santis
authors.forename: Laura
authors.initials: L
authors.lastname: Braccini
authors.forename: Federico
authors.initials: F
authors.lastname: Gulluni
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cancer; PI3K; PI3K inhibitors; Ras; mTOR; signaling