Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

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AKT/PKB signaling: navigating downstream

Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver

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Upstream and downstream of mTOR

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SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver

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The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation

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TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival

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AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

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Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma

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A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance

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TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

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mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery

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Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial

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Targeting the phosphoinositide 3-kinase pathway in cancer

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Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton

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mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt

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ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions

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Targeting PI3K signalling in cancer: opportunities, challenges and limitations

Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445

Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB

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Tumor cell metabolism: cancer's Achilles' heel

Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337

Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization

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The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin

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An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1

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Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.

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LKB1 is the upstream kinase in the AMP-activated protein kinase cascade

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Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway

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AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1

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Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex

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Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer

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The nuts and bolts of AGC protein kinases

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Phosphorylation and Functional Inactivation of TSC2 by Erk

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Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

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The TSC1–TSC2 complex: a molecular switchboard controlling cell growth

Huang, J., & Manning, B. D. (2008) · Biochemical Journal · doi:10.1042/bj20080281 · Cited by 1,237

The coordinate regulation of the p53 and mTOR pathways in cells

Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235

DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival

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Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells

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The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins

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Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

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The LKB1 tumor suppressor negatively regulates mTOR signaling

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Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb

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Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis

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The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy

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Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR

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Akt regulates growth by directly phosphorylating Tsc2

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PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest

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Randomized Phase II Study of Multiple Dose Levels of CCI-779, a Novel Mammalian Target of Rapamycin Kinase Inhibitor, in Patients With Advanced Refractory Renal Cell Carcinoma

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The PTEN–PI3K pathway: of feedbacks and cross-talks

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mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

García-Martínez, J. M., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20081668 · Cited by 907

The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis

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Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression

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Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

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AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity

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NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations

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Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase

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Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction

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Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling

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Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study

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Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study

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An Emerging Role of mTOR in Lipid Biosynthesis

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mTOR·RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes

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Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

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Targeting the mTOR Signaling Network for Cancer Therapy

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Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor–Positive Breast Cancer

Baselga, J. M., Семиглазов, В. Ф., van Dam, P., Manikhas, A., Bellet, M., Mayordomo, J. I., Campone, M., Kubista, E., Greil, R., Bianchi, G., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.8391 · Cited by 639

Rapamycin causes regression of astrocytomas in tuberous sclerosis complex

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The NF1 tumor suppressor critically regulates TSC2 and mTOR

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Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer

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An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten +/− mice

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The Structure of a Human p110α/p85α Complex Elucidates the Effects of Oncogenic PI3Kα Mutations

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Increased Activation of the Mammalian Target of Rapamycin Pathway in Liver and Skeletal Muscle of Obese Rats: Possible Involvement in Obesity-Linked Insulin Resistance

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Targeting phosphoinositide 3-kinase—Moving towards therapy

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ATP citrate lyase is an important component of cell growth and transformation

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AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer

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Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma

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p27 Kip1 modulates cell migration through the regulation of RhoA activationPreprint

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mTOR Complex1–S6K1 signaling: at the crossroads of obesity, diabetes and cancer

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Dose- and Schedule-Dependent Inhibition of the Mammalian Target of Rapamycin Pathway With Everolimus: A Phase I Tumor Pharmacodynamic Study in Patients With Advanced Solid Tumors

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Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

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Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

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PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP

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mTORC1-Activated S6K1 Phosphorylates Rictor on Threonine 1135 and Regulates mTORC2 Signaling

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Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1

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Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1

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Cancer-specific mutations in PIK3CA are oncogenic in vivo

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Inhibition of mTOR Activity Restores Tamoxifen Response in Breast Cancer Cells with Aberrant Akt Activity

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