Abstract
In this issue of Cancer Cell, Phung and coworkers demonstrate that sustained endothelial activation of Akt by expression of constitutively activated Akt1 (myrAkt1) leads to blood vessels that essentially recapitulate the complex structural and functional abnormalities of tumor vessels. The authors provide evidence that rapamycin inhibition of PI3K/Akt/mTOR signaling in endothelial cells (ECs), by either reducing Akt activity or blocking mTOR, reverses the pathologic effects associated with excess VEGF signaling in the tumor vasculature. However, unexpected findings following mTOR inhibition in vivo highlight the seemingly paradoxical and complex effects of rapamycin on various cell types within the tumor microenvironment.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
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Comment
MeSH terms
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Antibiotics, Antineoplastic / pharmacology*
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Endothelial Cells / drug effects*
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Endothelial Cells / physiology
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / pathology
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Enzyme Activation
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Humans
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Neoplasms / blood supply*
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Neovascularization, Pathologic / pathology*
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Phosphatidylinositol 3-Kinases / physiology
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Phosphorylation
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Protein Kinases / physiology
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / physiology
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Signal Transduction
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Sirolimus / pharmacology*
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TOR Serine-Threonine Kinases
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A / physiology
Substances
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Antibiotics, Antineoplastic
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Vascular Endothelial Growth Factor A
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Protein Kinases
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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Sirolimus