Dual mTORC2/mTORC1 Targeting Results in Potent Suppressive Effects on Acute Myeloid Leukemia (AML) Progenitors

No abstract is available for this paper.

• Publication year

  2011

• Venue

  Clinical Cancer Research

• Publication date

  2011-03-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1158/1078-0432.CCR-10-2285PMID 21415215PMCID PMC3131493
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2011cited by this paper
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  2010cited by this paper
• Exploiting cellular pathways to develop new treatment strategies for AML.

  2010cited by this paper
• Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor

  2010cited by this paper
• Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells

  2010cited by this paper
• CNK1 is a novel Akt interaction partner that promotes cell proliferation through the Akt-FoxO signalling axis

  2010cited by this paper
• Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses

  2009cited by this paper
• An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1*

  2009cited by this paper
• TOR complex 2: a signaling pathway of its own.

  2009influential reference
• Targeting the PI3K/AKT/mTOR signaling network in acute myelogenous leukemia

  2009cited by this paper
• A Phase I Study of the Mammalian Target of Rapamycin Inhibitor Sirolimus and MEC Chemotherapy in Relapsed and Refractory Acute Myelogenous Leukemia

  2009influential reference
• TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2.

  2009cited by this paper
• Targeting mTOR globally in cancer: Thinking beyond rapamycin

  2009cited by this paper
• Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy

  2009cited by this paper
• Everolimus (RAD001): an mTOR inhibitor for the treatment of metastatic renal cell carcinoma

  2009cited by this paper
• The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia

  2009cited by this paper
• Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia.

  2009influential reference
• Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways.

  2008cited by this paper
• Role of the Akt pathway in mRNA translation of interferon-stimulated genes

  2008cited by this paper
• Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model.

  2008cited by this paper
• Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer.

  2008cited by this paper
• Exploiting the mammalian target of rapamycin pathway in hematologic malignancies

  2008cited by this paper
• Regulatory Effects of Mammalian Target of Rapamycin-mediated Signals in the Generation of Arsenic Trioxide Responses*

  2008cited by this paper
• Suppression of Programmed Cell Death 4 (PDCD4) Protein Expression by BCR-ABL-regulated Engagement of the mTOR/p70 S6 Kinase Pathway*

  2008cited by this paper
• Pharmacokinetic and Tumor Distribution Characteristics of Temsirolimus in Patients with Recurrent Malignant Glioma

  2007cited by this paper
• Defining the role of mTOR in cancer.

  2007cited by this paper
• Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.

  2007cited by this paper
• Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.

  2007cited by this paper
• The two TORCs and Akt.

  2007influential reference
• The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

  2006cited by this paper
• S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth

  2006cited by this paper
• Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways

  2006cited by this paper
• Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia

  2006cited by this paper
• Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.

  2006cited by this paper
• S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.

  2006cited by this paper
• Mechanisms of type-I- and type-II-interferon-mediated signalling

  2005cited by this paper
• Activation of AKT kinases in cancer: implications for therapeutic targeting.

  2005cited by this paper
• The Akt-mTOR tango and its relevance to cancer.

  2005cited by this paper
• PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kB, MAPkinase and p53 pathways

  2005cited by this paper
• Differential regulation of the p70 S6 kinase pathway by interferon alpha (IFNalpha) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells.

  2005cited by this paper
• AKT/PKB signaling mechanisms in cancer and chemoresistance.

  2005cited by this paper
• Differential regulation of the p70 S6 kinase pathway by interferon α (IFNα) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells

  2005cited by this paper
• mTOR regulates cell survival after etoposide treatment in primary AML cells.

  2005cited by this paper
• Drug therapy for acute myeloid leukemia.

  2005cited by this paper
• Gatekeeper pathways and cellular background in the pathogenesis and therapy of AML

  2005cited by this paper
• Upstream and downstream of mTOR.

  2004influential reference
• Balancing Akt with S6K

  2004cited by this paper
• In vitro efficacy of combined treatment depends on the underlying mechanism of resistance in imatinib-resistant Bcr-Abl-positive cell lines.

  2004cited by this paper
• Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer.

  2004cited by this paper
• Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment.

  2003cited by this paper
• The Transformation Suppressor Pdcd4 Is a Novel Eukaryotic Translation Initiation Factor 4A Binding Protein That Inhibits Translation

  2003cited by this paper
• Survival of acute myeloid leukemia cells requires PI3 kinase activation.

  2003cited by this paper
• Focus on acute leukemias.

  2002cited by this paper
• Hierarchical phosphorylation of the translation inhibitor 4E-BP1.

  2001cited by this paper
• Activation of Rac1 and the p38 Mitogen-activated Protein Kinase Pathway in Response to All-trans-retinoic Acid*

  2001cited by this paper
• Acute myeloid leukemia.

  1999cited by this paper
• 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway.

  1998cited by this paper
• Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo.

  1997cited by this paper

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• Development of a SIN1 targeting inhibitor as a novel therapeutic approach for the treatment of malignancies.

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• PDCD4: A critical regulator in leukemic signaling networks and its therapeutic potential

  2025cites this paper
• Integrated systems biology analysis of acute lymphoblastic leukemia: unveiling molecular signatures and drug repurposing opportunities

  2024cites this paper
• Targeting metabolism: A potential strategy for hematological cancer therapy

  2022cites this paper
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  2022cites this paper
• Suppression of MYC by PI3K/AKT/mTOR pathway inhibition in combination with all‐trans retinoic acid treatment for therapeutic gain in acute myeloid leukaemia

  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• Phase Ib study of the mTOR inhibitor everolimus with low dose cytarabine in elderly acute myeloid leukemia

  2018cites this paper
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  2017influential citation
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  2017cites this paper
• Role of mTORC1-S6K1 signaling pathway in regulation of hematopoietic stem cell and acute myeloid leukemia.

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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• The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia: a phase Ib/II study

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• [Advances in leukemia inhibitors targeting PI3K/AKT/mTOR pathway].

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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2012cites this paper
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  2012cites this paper
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