title: An overview of the mTOR pathway as a target in cancer therapy.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) signaling cascade is a key regulatory pathway controlling initiation of mRNA translation in mammalian cells. The mTOR inhibitor rapamycin and its derivatives have shown potent antineoplastic activities in many preclinical models and clinical trials. First-generation mTOR inhibitors are now FDA-approved for the treatment of renal cell carcinoma.
  
  
  METHODS
  This article reviews the components of the mTOR pathway and their normal functions, highlighting the most common alterations in the pathway, seen in various human malignancies. It also discusses elements and effectors of this signaling cascade and reviews the therapeutic relevance of pharmacological inhibitors of the pathway in several malignancies, including lymphomas, leukemias, sarcomas, renal cell carcinoma, and breast cancer.
  
  
  CONCLUSIONS
  mTOR targeting is a highly promising therapeutic approach. First-generation mTOR inhibitors have already shown substantial activity in the treatment of certain tumors, while the emergence of second-generation catalytic mTOR inhibitors provides a better approach to target the pathway in malignant cells and has raised the potential for better clinical outcomes in the future.
authors.affiliation: Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center , 303 East Superior Street, Lurie 3-107, Chicago, IL 60611 , USA +1 312 5034267 ; +1 312 9081372 ; l-platanias@northwestern.edu.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Gentzler
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Altman
authors.forename: Leonidas C
authors.initials: LC
authors.lastname: Platanias
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014176:Protein Biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases