title: The Mammalian target of rapamycin inhibitors in breast cancer: current evidence and future directions.
abstract: Mammalian target of rapamycin (mTOR) is a crucial mediator of tumor progression and may be a promising target in a significant proportion of patients with breast cancer. More specifically, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway plays a critical role in multiple cellular functions including metabolism, proliferation, growth and survival. This pathway is higly active in many types of cancer and is linked to resistance to many types of therapy. Direct blockade of the mTOR pathway is a new area in breast cancer therapy, with the potential to modulate growth factor- and estrogen-dependent and estrogen-independent pathways, which contribute to the pathogenesis and progression of tumors. Thus, inhibitors of mTOR are of interest as potential therapeutic agents for patients with breast cancer, everolimus and temsirolimus being the main representatives of this category. This review of the literature analyzes the available data emerging from trials and evaluates the efficacy and safety of mTOR inhibitors in all subtypes of breast cancer.
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Malaguti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Vari
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004967:Estrogens / Q000378:metabolism; D000068338:Everolimus; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004967:Estrogens; D000068338:Everolimus; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C401859:temsirolimus; C546842:MTOR protein, human; C508053:ERBB2 protein, human