title: Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer.
abstract: While PI3K/AKT/mTOR pathway is altered in a variety of cancers including non small cell lung cancer, abnormalities in this pathway are more common in squamous cell lung carcinoma than in adenocarcinoma of the lung. Moreover, aberrant activation of PI3K/AKT/mTOR pathway is one of the mechanisms of acquired resistance to EGFR-TK inhibitors in patients with adenocarcinoma carrying EGFR activating mutations. Several inhibitors of the PI3K pathway are undergoing evaluation in preclinical and clinical studies. These include pan and selective inhibitors of PI3K, AKT inhibitors, rapamycin and rapalogs for mTOR inhibition, dual mTORC1-mTORC2 inhibitors and dual PI3K-mTOR inhibitors. This review focuses on recent preclinical and clinical data on the efficacy of PI3K pathway inhibitors in NSCLC either as monotherapy approach or in combination with chemotherapy or with drugs that target other signaling transduction pathways.
authors.affiliation: Unit of Experimental Oncology, Clinical and Experimental Medicine Department, University of Parma, Via Volturno 39, 43126 Parma, Italy. Electronic address: claudia.fumarola@unipr.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fumarola
authors.affiliation: Unit of Experimental Oncology, Clinical and Experimental Medicine Department, University of Parma, Via Volturno 39, 43126 Parma, Italy. Electronic address: mara.bonelli@unipr.it.
authors.forename: Mara A
authors.initials: MA
authors.lastname: Bonelli
authors.affiliation: Unit of Experimental Oncology, Clinical and Experimental Medicine Department, University of Parma, Via Volturno 39, 43126 Parma, Italy. Electronic address: piergiorgio.petronini@unipr.it.
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Petronini
authors.affiliation: Unit of Experimental Oncology, Clinical and Experimental Medicine Department, University of Parma, Via Volturno 39, 43126 Parma, Italy. Electronic address: roberta.alfieri@unipr.it.
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Alfieri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: AKT; NSCLC; PI3K; SQCLC; mTOR