title: Clinical development of mTOR inhibitors in breast cancer.
abstract: The mammalian target of rapamycin (mTOR) pathway is a central pathway that regulates mRNA translation, protein synthesis, glucose metabolism, lipid synthesis and autophagy, and is involved in malignant transformation. Several randomized trials have shown that the use of mTOR inhibitors could improve patient outcome with hormone receptor-positive or human epidermal growth factor receptor-2-positive breast cancer. This review analyzes new perspectives from these trials. Preclinical studies have suggested that the mTOR pathway may play a role in the resistance to hormone therapy, trastuzumab and chemotherapy for breast cancer. This concept has been tested in clinical trials for neoadjuvant treatment and for metastatic breast cancer patients. Also, much effort has gone into the identification of biomarkers that will allow for more precise stratification of patients. Findings from these studies will provide indispensable tools for the design of future clinical trials and identify new perspectives and challenges for researchers and clinicians.
authors.forename: Cecile
authors.initials: C
authors.lastname: Vicier
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Dieci
authors.forename: Monica
authors.initials: M
authors.lastname: Arnedos
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Fabrice
authors.initials: F
authors.lastname: Andre
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068338:Everolimus; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000068878:Trastuzumab; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068338:Everolimus; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab; C546842:MTOR protein, human; C508053:ERBB2 protein, human