title: Roles of EGFR, PI3K, AKT, and mTOR in heavy metal-induced cancer.
abstract: Humans are exposed to heavy metals through a variety of occupational and non-occupational means. Growing evidence has accumulated that prolonged exposure to these heavy metals is associated with cancer occurrence at various body sites including lung, liver, bladder, colon, and skin. Much research effort has been placed on discovering the mechanisms by which heavy metals induce different kinds of cancers. Results from these mechanistic studies have varied for different metals, but increased activation of signaling pathways is often observed. This review will focus on the signaling molecules including epidermal growth factor receptor (EGFR), phosphatidyl inositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR) in carcinogenesis and cancer progression; and how these molecules are affected by the exposure to heavy metals: arsenic, chromium, nickel, and cadmium. Furthermore, drug targets for the prevention and therapy of cancers induced by heavy metals will be discussed with a focus on drugs that are currently in clinical trials for these targets.
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Carpenter
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D019216:Metals, Heavy / Q000633:toxicity*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019216:Metals, Heavy; D009363:Neoplasm Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1