title: Review of PI3K/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers.
abstract: BACKGROUND
  Constitutive activation of the PI3K/mTOR signaling pathway is observed in most, if not all, breast cancers. Accordingly, many PI3K and/or mTOR inhibitors have entered clinical trials, and completed studies should soon reveal the efficacy of these new drug families in the treatment of cancer patients.
  
  
  OBJECTIVE
  We present the PI3K/Akt/mTOR signaling pathway and the structure and the anti-tumor efficiency of some mTOR inhibitors such as rapalogues and competitive inhibitors, which have entered clinical trials. We also discuss some of the clinical trial results associated with these molecules mainly focusing on studies performed on relapsing breast cancer patients - but not only.
  
  
  RESULTS
  Most of the clinical trials with PI3K/mTOR inhibitors alone or in combination with chemotherapies were performed in heavily pre-treated patients and revealed non-negligible amounts of partial responses and long-term stable disease for these patients. Therefore, these compounds seem to prevent tumor growth and survival of cancer cells in Human, representing a new range of anti-tumor drugs that can be utilized not only as first-line treatments but as second- and third-line agents for patients who relapse.
  
  
  CONCLUSIONS
  Drugs inhibiting the PI3K/mTOR signaling pathway may represent tailored anti-tumor agents, paving the way for their clinical application in different tumor types.
authors.forename: Amélie
authors.initials: A
authors.lastname: Fouqué
authors.forename: Mickael
authors.initials: M
authors.lastname: Jean
authors.forename: Pierre van de
authors.initials: Pv
authors.lastname: Weghe
authors.affiliation: Centre Eugène Marquis, INSERM ERL440, Rue Bataille Flandres Dunkerque, 35042 Rennes, France. patrick.legembre@inserm.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Legembre
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D005260:Female; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D058570:TOR Serine-Threonine Kinases