title: Biologic impact and clinical implication of mTOR inhibition in metastatic breast cancer.
abstract: ABSTRACTThe goal of therapy for patients with metastatic breast cancer (MBC) is prolonging life and palliation of symptoms. Thus the preferred approach remains to use, at least initially, non-cytotoxic drugs. In hormone receptor-positive breast cancer the sequential use of single anti-estrogen drugs, e.g. tamoxifen, aromatase inhibitors, and many others is standard, but eventually drug resistance will lead to failure of these compounds and a switch to chemotherapy will be necessary. Reversing resistance to anti-estrogen therapy in MBC is one of the strategies to avoid and delay the use of cytotoxic compounds. The mammalian target of rapamycin (mTOR) has been recently associated with in vitro reversal of drug resistance, including tamoxifen resistance. A number of early clinical studies have confirmed the concept and, more recently, everolimus was successfully tested in a randomized controlled trial in postmenopausal patients who progressed on previous anti-estrogen therapy for MBC. This manuscript will review the biology, preclinical and clinical data including the randomized controlled trial that lead to the approval of everolimus by the US FDA.
authors.affiliation: 1Sylvester Comprehensive Cancer Center, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida - USA.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Westin
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Perez
authors.forename: Emilie
authors.initials: E
authors.lastname: Wang
authors.forename: Stefan
authors.initials: S
authors.lastname: Glück
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases