title: Next generation of mammalian target of rapamycin inhibitors for the treatment of cancer.
abstract: BACKGROUND
  Because of the central role of the mammalian target of rapamycin (mTOR) pathway in the control and distribution of signals essential for mRNA translation of mitogenic genes and generation of oncogenic proteins, effective targeting of mTOR remains a major goal in medical oncology.
  
  
  METHODS
  This article summarizes preclinical and clinical studies relating to the next generation of mTOR inhibitors. While rapalogs have shown activity in the treatment of breast, renal and neuroendocrine tumors, these agents do not block mTORC2, one of the two major protein complexes in which mTOR participates. In addition, there is emerging evidence that these agents only partially block mTORC1, underscoring the need for more effective mTOR inhibitors. In recent years, catalytic mTOR inhibitors have been developed, which block both mTORC1 and mTORC2. Such inhibitors show generally better activity in preclinical models than rapalogs and some of them have been or are in clinical trials in humans.
  
  
  CONCLUSIONS
  It is anticipated that with the continuous expansion of work in this research field, the therapeutic potential of targeting the mTOR pathway for the treatment of several malignancies will reach a maximum point in the next few years and may ultimately change the way we treat several malignant tumors.
authors.affiliation: Northwestern University Medical School, Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, 303 East Superior Street, Lurie 3-107, Chicago, IL 60611, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Nelson
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; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases