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.
MeSH terms
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Animals
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Antibodies, Monoclonal, Humanized / therapeutic use*
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Clinical Trials as Topic
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Drug Evaluation, Preclinical
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Drug Resistance, Neoplasm
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Everolimus
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Female
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Humans
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Neoplasm Metastasis
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Phosphatidylinositol 3-Kinases / metabolism
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Receptor, ErbB-2 / metabolism
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Signal Transduction / drug effects
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Sirolimus / adverse effects
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Sirolimus / analogs & derivatives*
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Sirolimus / pharmacology
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Sirolimus / therapeutic use
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TOR Serine-Threonine Kinases / metabolism
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Trastuzumab
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Treatment Outcome
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Everolimus
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Receptor, ErbB-2
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TOR Serine-Threonine Kinases
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Trastuzumab
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Sirolimus