Abstract
The mammalian target of rapamycin (mTOR) is frequently activated in epithelial ovarian cancer, and is regarded as an attractive therapeutic target for therapy. Preclinical investigations using rapamycin and its analogs have demonstrated significant growthinhibitory effects on the growth of ovarian cancer both in the setting of monotherapy and in combination with cytotoxic agents. Based on promising preclinical data, mTOR inhibitors are currently being evaluated in several phase I/II trials in patients with ovarian cancer. In an effort to overcome resistance to rapamycin and its analogs, the novel ATP-competitive mTOR inhibitors have recently been developed. In this report, we review the scientific rationale and evidence for the potential clinical benefits provided by mTOR inhibitor therapy for patients with epithelial ovarian cancer.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Carcinoma, Ovarian Epithelial
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Catalytic Domain / drug effects
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Female
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Humans
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Neoplasms, Glandular and Epithelial / drug therapy*
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Neoplasms, Glandular and Epithelial / enzymology
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / enzymology
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Signal Transduction / drug 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 / antagonists & inhibitors*
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TOR Serine-Threonine Kinases / chemistry
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TOR Serine-Threonine Kinases / metabolism*
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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TOR Serine-Threonine Kinases
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Sirolimus