2011
DOI: 10.1172/jci44145
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Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

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Cited by 372 publications
(379 citation statements)
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References 151 publications
(161 reference statements)
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“…Its signals are complex, integrating many environmental cues (e.g., growth factors, energy/nutrients) to regulate important cellular processes (e.g., autophagy, macromolecule biosynthesis) (Laplante & Sabatini, 2012). mTOR inhibitors are approved to treat some cancers, with presumed effects on cancer cell proliferation or metabolism, and with many new mTOR inhibitors in development or in clinical trials (Wander et al ., 2011). …”
Section: Introductionmentioning
confidence: 99%
“…Its signals are complex, integrating many environmental cues (e.g., growth factors, energy/nutrients) to regulate important cellular processes (e.g., autophagy, macromolecule biosynthesis) (Laplante & Sabatini, 2012). mTOR inhibitors are approved to treat some cancers, with presumed effects on cancer cell proliferation or metabolism, and with many new mTOR inhibitors in development or in clinical trials (Wander et al ., 2011). …”
Section: Introductionmentioning
confidence: 99%
“…mTORC1/C2 complexes share common members but possess also specific elements such as Raptor (in mTORC1) and Rictor (in mTORC2). 10,11 Activated mTOR phosphorylates key translational regulators: initiation factor 4E-binding protein (4EBP1), 70 kDa S6 ribosomal protein kinase (p70S6K) and subsequently ribosomal S6 protein. 12 mTORC1 is sensitive to currently used mTOR inhibitors (rapamycin, temsirolimus and everolimus).…”
mentioning
confidence: 99%
“…The growing complexity of the mTOR pathway, as well as emerging discoveries about its autoregulatory mechanisms and activating feedback loops (4,9), highlights the need for ongoing research of the mTOR pathway in multiple myeloma. Our data aligned with previous findings in multiple myeloma (10) suggest that targeting mTOR kinase produces more effective mTOR pathway inhibition than rapamycin with a more detrimental impact on multiple myeloma cells.…”
Section: Discussionmentioning
confidence: 99%
“…The observed mTORC2 activation of Akt following rapamycin treatment prompted the rapid development of mTOR kinase inhibitors (9). On the basis of recent preclinical testing of mTOR kinase in multiple myeloma (10), it was predicted that reduction in phosphorylated (p) 4E-BP1 and p-Akt, both refractory to rapamycin, may provide preliminary evidence of mTOR kinase target inhibition and may overcome rapamycinrelated resistance mechanisms.…”
Section: Introductionmentioning
confidence: 99%