title: Everolimus and its role in hormone-resistant and trastuzumab-resistant metastatic breast cancer.
abstract: Advances in targeted therapies have improved progression-free and overall survival in women with metastatic breast cancer; however, regardless of efficacy, resistance almost always occurs eventually. Upregulation of the PI3K/AKT/mTOR pathway, which promotes cell growth and proliferation, is a means of escaping responsiveness to hormone therapy in hormone receptor-positive disease, or trastuzumab in HER2-positive disease. Everolimus, an inhibitor of mTOR, has shown promise in early clinical trials in metastatic breast cancer and is currently being studied in larger Phase II and III clinical trials, combined with hormone therapy or trastuzumab with or without cytotoxic chemotherapy. In this article, we discuss the mechanistic and preclinical data for everolimus, efficacy and safety results of clinical trials, and the landscape looking forward.
authors.affiliation: University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, 2nd floor, San Francisco, CA 94115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Keck
authors.forename: Alexa C
authors.initials: AC
authors.lastname: Glencer
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068338:Everolimus; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab