Targeted therapy in sarcomas: mammalian target of rapamycin inhibitors from bench to bedside. (scientific article published on 20 October 2011)

[18F]fluorodeoxyglucose positron emission tomography correlates with Akt pathway activity but is not predictive of clinical outcome during mTOR inhibitor therapy.

Q37210960

Protein kinase A and TORC1 activate genes for ribosomal biogenesis by inactivating repressors encoded by Dot6 and its homolog Tod6.

Q37415934

Targeting the mTOR pathway using deforolimus in cancer therapy

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Targeting sarcomas: novel biological agents and future perspectives

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mTOR signaling and drug development in cancer

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mTOR Mediated Anti-Cancer Drug Discovery

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A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer.

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ER stress inhibits mTORC2 and Akt signaling through GSK-3β-mediated phosphorylation of rictor.

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Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas

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Ezrin mediates growth and survival in Ewing’s sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway

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Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2

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Ubiquitination regulates PTEN nuclear import and tumor suppression

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Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis

Q24293735

Activation of mTORC2 by association with the ribosome

Q24294876

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

Q24295120

Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton

Q24299873

mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery

Q24302549

Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action

Q24302566

Requirement of the mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells

Q24303535

Identification of Protor as a novel Rictor-binding component of mTOR complex-2

Q24303936

SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth

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

Q24311448

The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1

Q24315566

mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1

Q24319851

IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway

Q24337225

Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner

Q24337323

Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin.

Q24540159

Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth

Q24603549

Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator

Q24609227

A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

Q24629627

A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

Q24632651

mTOR regulates memory CD8 T-cell differentiation

Q24648624

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray

Q24657451

The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo

Q24657924

Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study

Q36454797

Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors

Q36486421

Therapeutic targets: MTOR and related pathways

Q36592032

Targeted therapy for dermatofibrosarcoma protuberans

Q36718629

Gene expression profiling in sarcomas

Q36843032

Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study

Q36856816

The biology behind mTOR inhibition in sarcoma

Q36927347

PTEN loss in the continuum of common cancers, rare syndromes and mouse models.

Q37856722

Temsirolimus in advanced leiomyosarcomas: patterns of response and correlation with the activation of the mammalian target of rapamycin pathway

Q38412112

Cell surface expression of epidermal growth factor receptor and Her-2 with nuclear expression of Her-4 in primary osteosarcoma

Q38448504

Antitumor activity of ridaforolimus and potential cell-cycle determinants of sensitivity in sarcoma and endometrial cancer models

Q39463504

Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin

Q39524587

MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration

Q39526077

Chromatin structure predicts epigenetic therapy responsiveness in sarcoma

Q39610375

Phosphatidylinositol-3'-kinase/AKT signaling is essential in synovial sarcoma.

Q39624408

Zoledronic acid potentiates mTOR inhibition and abolishes the resistance of osteosarcoma cells to RAD001 (Everolimus): pivotal role of the prenylation process.

Q39640530

mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes

Q39758212

mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling

Q39765614

Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin

Q39827828

Conditioned media from mouse osteosarcoma cells promote MC3T3-E1 cell proliferation using JAKs and PI3-K/Akt signal crosstalk

Q39924288

KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway

Q40124442

Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif

Q40133024

Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma

Q40200306

The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor

Q40244438

Functional genomics identifies TOR-regulated genes that control growth and division

Q40277449

Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing's sarcoma

Q40417879

Alternative phospholipase D/mTOR survival signal in human breast cancer cells

Q40484574

Mechanism of action of the immunosuppressant rapamycin

Q40965429

SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo

Q41099411

A phase I-II study of everolimus (RAD001) in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors

Q43052325

Rapamycin for Kaposi's sarcoma and graft-versus-host disease in bone marrow transplant recipient

Q43136394

Treatment with the mTOR inhibitor temsirolimus in patients with malignant PEComa

Q43136879

AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity

Q43211411

Hybrid inhibitors of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR): design, synthesis, and superior antitumor activity of novel wortmannin-rapamycin conjugates

Q43237952

Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor

Q43873032

Adjuvant chemotherapy in 2011 for patients with soft-tissue sarcoma

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Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies

Q45067792

Targeting the mammalian target of rapamycin in myxoid chondrosarcoma.

Q46338130

Expression of epidermal growth factor receptor, ERBB2 and KIT in adult soft tissue sarcomas: a clinicopathologic study of 281 cases

Q46385316

Phospho-S6 ribosomal protein: a potential new predictive sarcoma marker for targeted mTOR therapy

Q46834814

Anticancer effect of sirolimus in renal allograft recipients with de novo malignancies

Q46894274

Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma

Q46973585

Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism.

Q51803667

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

Q24672005

A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling

Q24678327

Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation

Q27671542

Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP

Q27732817

TSC2 mediates cellular energy response to control cell growth and survival

Q27860970

Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors

Q28118852

Phosphatidic acid-mediated mitogenic activation of mTOR signaling

Q28208274

PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells

Q28237807

The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer

Q28244254

SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity

Q28262782

Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1

Q28276788

Autophagy and signaling: their role in cell survival and cell death

Q28278893

DNA hypermethylation status of multiple genes in soft tissue sarcomas

Q28279569

Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells

Q28305483

Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB

Q28306356

Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target of rapamycin complex 1 (mTORC1)

Q28478869

Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1

Q28505561

mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt

Q29547767

An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1

Q29614563

Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E

Q29618009

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

Q29618031

Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma

Q29618608

Akt regulates growth by directly phosphorylating Tsc2

Q29620397

mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway

Q30425628

mTORC2 regulates neutrophil chemotaxis in a cAMP- and RhoA-dependent fashion

Q30499352

EGFR-dependent and independent activation of Akt/mTOR cascade in bone and soft tissue tumors

Q33273472

Ribosomal S6 kinase signaling and the control of translation

Q33783527

E2F1 regulates cellular growth by mTORC1 signaling

Q33808832

Targeted morphoproteomic profiling of Ewing's sarcoma treated with insulin-like growth factor 1 receptor (IGF1R) inhibitors: response/resistance signatures

Q33873775

Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma

Q33895137

The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling.

Q33928657

Regulation of mTORC1 signaling by pH

Q33955047

Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial

Q34041573

Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase.

Q34063643

Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway

Q34085728

Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation

Q34109986

PDGFRA activating mutations in gastrointestinal stromal tumors.

Q34169772

Tuberous sclerosis: from tubers to mTOR.

Q34173640

Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size

Q34176565

Clinical pharmacokinetics of sirolimus

Q34347243

Everolimus for advanced pancreatic neuroendocrine tumors.

Q34399809

Prostaglandin E2 activates and utilizes mTORC2 as a central signaling locus for the regulation of mast cell chemotaxis and mediator release

Q34452585

The Pim protein kinases regulate energy metabolism and cell growth

Q34490450

Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus

Q34532986

Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules

Q34610473

A continuum model for tumour suppression

Q34631552

miRNA Profiling: How to Bypass the Current Difficulties in the Diagnosis and Treatment of Sarcomas

Q34700668

Phosphatidylserine is a critical modulator for Akt activation

Q34712409

Phospholipase D1 is an effector of Rheb in the mTOR pathway.

Q34786317

mTOR complex 2 targets Akt for proteasomal degradation via phosphorylation at the hydrophobic motif.

Q34800160

IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation.

Q34836259

Control of mTORC1 signaling by the Opitz syndrome protein MID1.

Q35008479

Relieving autophagy and 4EBP1 from rapamycin resistance

Q35096637

PI3Kγ mediates kaposi's sarcoma-associated herpesvirus vGPCR-induced sarcomagenesis.

Q35207596

Mechanisms of sarcoma development

Q35210018

Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway

Q35213308

Phosphatidic acid activates mammalian target of rapamycin complex 1 (mTORC1) kinase by displacing FK506 binding protein 38 (FKBP38) and exerting an allosteric effect

Q35313512

Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling

Q35370616

PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR

Q35613890

Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.

Q35751042

A phase 2 study of temsirolimus (CCI-779) in patients with soft tissue sarcomas: a study of the Mayo phase 2 consortium (P2C).

Q35854468

Advances in sarcoma genomics and new therapeutic targets

Q35993346

Oncogenic PI3K deregulates transcription and translation