CoChat
Sign Up
Cited by 510

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health

Chappell, William H., Steelman, Linda S., Long, Jacquelyn M., Kempf, Ruth C., Abrams, Stephen L., Franklin, Richard A., Bäsecke, Jörg, Stivala, Franca, Donia, Marco, Fagone, Paolo, Malaponte, Graziella, Mazzarino, Maria C., Nicoletti, Ferdinando, Libra, Massimo, Maksimovic-Ivanic, Danijela, Mijatovic, Sanja, Montalto, Giuseppe, Cervello, Melchiorre, Laidler, Piotr, Milella, Michele, Tafuri, Agostino, Bonati, Antonio, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M., McCubrey, James A.·2011·Oncotarget
DOI 10.18632/oncotarget.240PMC PMC3260807
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.18632/oncotarget.240

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Fine-tuning of MEK/ERK pathway activation by natural bioactive compounds, such as flavonoids, appears to promote physiological responses of gene transcription/translation and cell growth/survival and, in turn, advance human health as neuroprotectants and cognitive enhancers.

    “Although sustained hyperactivation of MEK/ERK signaling is a prerequisite for malignant transformation or progression, the fine-tuning of this pathway activation by natural bioactive compounds, such as flavonoids, appears to promote physiological responses of gene transcription/translation and cell growth/survival and, in turn, advance human health as neuroprotectants and cognitive enhancers.48–51”

    From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [49]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 261

  1. Bonati, 2008, Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and JAK/STAT pathways to leukemia, Leukemia, 22, 686, 10.1038/leu.2008.26 · DOI
  2. Bonati, 2008, Targeting Survival Cascades Induced by Activation of Raf/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy, Leukemia, 22, 708, 10.1038/leu.2008.27 · DOI
  3. Steelman, 2008, Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors, Current Opinion in Investigational Drugs., 9, 614
  4. Libra, 2007, Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance, Biochem Biophys Acta, 773, 1263
  5. Sebolt-Leopold, 2006, BRAF mutation predicts sensitivity to MEK inhibition, Nature, 439, 358, 10.1038/nature04304 · DOI
  6. Pao, 2008, Genetic predictors of MEK dependence in non-small cell lung cancer, Cancer Res, 68, 9375, 10.1158/0008-5472.CAN-08-2223 · DOI
  7. Santoro, 2009, Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial, Expert Rev Anticancer Ther, 9, 739, 10.1586/era.09.41 · DOI
  8. Tran, 2007, Targeted inhibition of the extracellular signal-regulated kinases kinase pathway with AZD-6244 (ARRY-142886) in the treatment of hepatocellular carcinoma, Mol Cancer Ther, 6, 138, 10.1158/1535-7163.MCT-06-0436 · DOI
  9. Crespo, 2009, ERK dimmers and scaffold proteins: unexpected partners for a forgotten task, Cell Cycle, 8, 1007, 10.4161/cc.8.7.8078 · DOI
  10. Li, 2008, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity, Proc Natl Acad Sci USA, 105, 3041, 10.1073/pnas.0711741105 · DOI · Paper page
  11. Gambacorti-Passerini, 2008, BRAF silencing by short hairpin RNA or chemical blockade by PLX-4032 leads to different responses in melanoma and thyroid carcinoma cells, Mol Cancer Res, 6, 751, 10.1158/1541-7786.MCR-07-2001 · DOI
  12. Marais, 2010, Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF, Cell, 140, 209, 10.1016/j.cell.2009.12.040 · DOI
  13. Nicoletti, 2010, Emerging MEK Inhibitors, Exp Opin Emerging Drugs, 15, 203, 10.1517/14728210903282760 · DOI
  14. McCubrey, 2010, The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy, Cell Cycle, 9, 1781, 10.4161/cc.9.9.11483 · DOI
  15. Miner, 2009, RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer, Cancer Res., 69, 6839, 10.1158/0008-5472.CAN-09-0679 · DOI
  16. Mijatovic, 2011, Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways, J Cell Physiol
  17. Dudley, 2002, Identification of a novel mitogen-activated protein kinase kinase activation domain recognized by the inhibitor PD 184352, Mol Cell Biol, 22, 7593, 10.1128/MCB.22.21.7593-7602.2002 · DOI
  18. Cohen, 2000, Specificity and mechanism of action of some commonly used protein kinase inhibitors, Biochem J, 351, 95, 10.1042/bj3510095 · DOI
  19. Delaney, 2004, Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition, Nat Struct Mol Biol, 11, 1192, 10.1038/nsmb859 · DOI
  20. Hurley, 2007, Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor, Clin Cancer Res, 13, 1576, 10.1158/1078-0432.CCR-06-1150 · DOI
  21. LoRusso, 2007, Clinical experience of MEK inhibitors in cancer therapy, Biochem et Biophysica Acta, 1773, 1248, 10.1016/j.bbamcr.2006.11.009 · DOI
  22. Smith, 2007, AZD6244 (ARRY 142886) a potent inhibitor of mitogen-activated protein kinase/extracellular signal-related kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship and potential for combination in preclinical models, Mol Cancer Ther., 6, 2209, 10.1158/1535-7163.MCT-07-0231 · DOI
  23. Meyer, 2003, CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK), Semin Oncol, 30, 105, 10.1053/j.seminoncol.2003.08.012 · DOI
  24. Mitchell, 2004, Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small cell lung, breast, colon, and pancreatic cancer, J Clin Oncol, 22, 4456, 10.1200/JCO.2004.01.185 · DOI · Paper page
  25. Sebolt-Leopold, 2008, Advances in the development of cancer therapeutics directed against the Ras-mitogen-activated protein kinase pathway, Clin Cancer Res, 14, 3651, 10.1158/1078-0432.CCR-08-0333 · DOI
  26. Gadgeel, 2010, A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer, Clin Cancer Res., 16, 2450, 10.1158/1078-0432.CCR-09-1920 · DOI · Paper page
  27. Ricart, 2010, Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers, Clin Cancer Res., 16, 1924, 10.1158/1078-0432.CCR-09-1883 · DOI
  28. Tesfaigzi, 2009, How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer?, Cell Cycle, 8, 1168, 10.4161/cc.8.8.8147 · DOI
  29. Nicoletti, 2009, Emerging Raf Inhibitors, Exp Opin Emerging Drugs, 14, 633, 10.1517/14728210903232633 · DOI
  30. McCubrey, 2008, Akt Inactivates ERK causing decreased response to chemotherapeutic drugs in advanced CaP cells, Cell Cycle, 7, 631, 10.4161/cc.7.5.5416 · DOI
  31. Shujath, 2004, BAY 43-9006 Exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis, Cancer Research, 64, 7099, 10.1158/0008-5472.CAN-04-1443 · DOI
  32. Flaherty, 2009, Integrating BRAF/MEK inhibitors into combination therapy for melanoma, British J Can, 100, 431, 10.1038/sj.bjc.6604891 · DOI
  33. McMahon, 2007, A new mouse model to explore the initiation, progression, and therapy of BRafV600E-induced lung tumors, Genes & Development, 21, 379, 10.1101/gad.1516407 · DOI
  34. Cervello, 2010, Novel combination of celecoxib and proteasome inhibitor MG132 in human hepatocellular carcinoma provides synergistic anti tumor effects, Cell Cycle, 9, 1399, 10.4161/cc.9.7.11254 · DOI
  35. Sitzmann, 1997, Increased MAPK expression and activity in primary human hepatocellular carcinoma, Biochem Biophys Res Commun, 236, 54, 10.1006/bbrc.1997.6840 · DOI
  36. Schmidt, 2004, Multiple anticancer effects of blocking MEK-ERK signaling in hepatocellular carcinoma, J Am Coll Surg, 198, 410, 10.1016/j.jamcollsurg.2003.10.004 · DOI
  37. Schmidt, 2008, Targeting MEK is effective chemoprevention of hepatocellular carcinoma in TGF-alpha-transgenic mice, J Gastrointest Surg., 12, 30, 10.1007/s11605-007-0396-4 · DOI
  38. Andreeff, 2005, Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia, Leukemia, 29, 1543
  39. Di Raimondo, 2007, ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia, Blood, 109, 5473, 10.1182/blood-2006-05-021071 · DOI
  40. Stegmeier, 2009, PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers, Cancer Res, 69, 4286, 10.1158/0008-5472.CAN-08-4765 · DOI · Paper page
  41. Berry, 2009, In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase in basal-like breast cancer models, Clin Cancer Res, 15, 4649, 10.1158/1078-0432.CCR-09-0317 · DOI
  42. Martelli, 2009, Dual inhibition of class IA phosphatidylionsitol 3-kinase and mTOR as a new therapeutic option for T-cell acute lymphoblastic leukemia, Cancer Res, 69, 3520, 10.1158/0008-5472.CAN-08-4884 · DOI
  43. Cheng, 2004, Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt, Cancer Res, 64, 4394, 10.1158/0008-5472.CAN-04-0343 · DOI · Paper page
  44. Martelli, 2008, Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor (2S)-1-(1H-Indol-3-yl)-3-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxypropan2-amine (A443654) in T acute lymphoblastic leukemia, Molecular Pharmacology, 74, 884, 10.1124/mol.108.047639 · DOI
  45. Myers, 2006, The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and anoikis in squamous cell carcinoma of the head and neck, Oral Oncol, 42, 430, 10.1016/j.oraloncology.2005.09.011 · DOI
  46. Martelli, 2008, Synergistic proapoptotic activity of recombinant trail plus the akt inhibitor perifosine in acute myelogenous leukemia cells, Cancer Res, 68, 9394, 10.1158/0008-5472.CAN-08-2815 · DOI
  47. Ramalingam, 2009, Preoperative therapy for early-stage NSCLC: oppurtunities and challenges, Oncology, 23, 886
  48. Bouscary, 2009, Targeting translation in acute myeloid leukemia: a new paradigm for therapy?, Cell Cycle, 8, 3893, 10.4161/cc.8.23.10091 · DOI
  49. Nicoletti, 2010, Potential use of rapamycin in HIV infection, Br J Clin Pharmacol., 70, 784, 10.1111/j.1365-2125.2010.03735.x · DOI
  50. Furman, 2007, Phase I study of Everolimus in pediatric patients with refractory solid tumors, JCO, 25, 4806, 10.1200/JCO.2007.11.4017 · DOI
  51. Goncharova, 2009, PI3K/mTORC1 activation in hamartoma syndromes: therapeutic prospects, Cell Cycle, 8, 403, 10.4161/cc.8.3.7555 · DOI
  52. Gabriel, 2008, Identification and characterization of NVP-BEZ234, a new orally available dual PI3K/mTOR inhibitor with potent in vivo anti tumor activity, Mol Can Ther, 7, 1851, 10.1158/1535-7163.MCT-08-0017 · DOI · Paper page
  53. Sebti, 2010, Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT, Invest New Drugs.
  54. Shokat, 2009, Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2, PLoS Biol, 7, e38
  55. Demkow, 2007, Sorafenib in advanced clear-cell renal-cell carcinoma, N Engl J Med., 356, 2
  56. Robertson, 2005, Mutant V599E B-Raf regulates growth and vascular development of malignant melanoma tumors, Cancer Res, 65, 2412, 10.1158/0008-5472.CAN-04-2423 · DOI
  57. Robertson, 2006, Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases, Cancer Res, 66, 8200, 10.1158/0008-5472.CAN-06-0809 · DOI
  58. Arcaroli, 2010, Identification of predictive markers of response to the MEK1/2 inhibitor selumetinib (AZD6244) in K-ras-mutated colorectal cancer, Mol Cancer Ther., 3351
  59. Escudier, 2009, Renal cell carcinoma, Lancet., 373, 9669
  60. Mueller, 2002, Sirolimus inhibits growth of human hepatoma cells in contrast to tacrolimus, which promotes cell growth, Transplant Proc, 34, 1
  61. Lindner, 2005, Inhibition of mTOR suppresses experimental liver tumours, Anticancer Res, 25, 789
  62. Dufour, 2007, Vascular remodeling and antitumoral effects of mTOR inhibition in a rat model of hepatocellular carcinoma, J Hepatol, 46, 840, 10.1016/j.jhep.2006.11.021 · DOI
  63. Lindnér, 2008, Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer, Int J Clin Oncol, 13, 66, 10.1007/s10147-007-0733-3 · DOI
  64. Wacheck, 2007, Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation, Transplantation, 83, 425, 10.1097/01.tp.0000252780.42104.95 · DOI
  65. Dammacco, 2007, In vivo inhibition of human hepatocellular carcinoma related angiogenesis by vinblastine and rapamycin, Histol Histopathol, 22, 285
  66. Doroshow, 2005, CCI-779 in metastatic melanoma: a phase II trial of the California cancer consortium, Cancer, 104, 1045, 10.1002/cncr.21265 · DOI
  67. Slingluff CL, 2003, Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor rapamycin, J Transl Med, 3, 39
  68. Kaur, 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H104R murine lung cancers, Nat Med, 14, 1351, 10.1038/nm.1890 · DOI · Paper page
  69. Tang, 2008, Effects of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma, Clin Cancer Res, 14, 5124, 10.1158/1078-0432.CCR-07-4774 · DOI
  70. McDaid, 2007, Targeting protein translation in human non-small cell lung cancer via combined MEK and mammalian target of rapamycin suppression, Cancer Res, 67, 11300, 10.1158/0008-5472.CAN-07-0702 · DOI
  71. Flaherty, 2006, Chemotherapy and targeted therapy combinations in advanced melanoma, Clin Cancer Res, 12, 2366s, 10.1158/1078-0432.CCR-05-2505 · DOI
  72. Langouët, 2007, GATA-1 is essential in EGF-meditated induction of nucleotide excision repair activity and ERCCI expression through ERK2 in human hepatoma cells, Cancer Res, 67, 2114, 10.1158/0008-5472.CAN-06-3821 · DOI
  73. Horwitz, 2005, Enhancement of the therapeutic efficacy of taxol by the mitogen-activated protein kinase kinase inhibitor CI-1040 in nude mice bearing human heterotransplants, Cancer Res, 65, 2854, 10.1158/0008-5472.CAN-04-4391 · DOI
  74. Smalley, 2008, The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY 142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel, Clin Cancer Res, 14, 230, 10.1158/1078-0432.CCR-07-1440 · DOI
  75. Saltz, 2010, Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial, JAMA., 304, 2154, 10.1001/jama.2010.1672 · DOI
  76. Nishio, 2002, Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel, J Biol Chem, 277, 33490, 10.1074/jbc.M204042200 · DOI
  77. Dennis, 2002, Variable apoptotic response of NSCLC cells to inhibition of the MEK/ERK pathway by small molecules or dominant negative mutants, Cell Death Differ, 9, 893, 10.1038/sj.cdd.4401054 · DOI
  78. Nakashima, 2004, Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma, Oncol Rep, 11, 375
  79. Rieber, 2006, Signalling responses linked to betulinic acid-induced apoptosis are antagonized by MEK inhibitor U0126 in adherent or 3D spheroid melanoma irrespective of p53 status, Int J Cancer, 118, 1135, 10.1002/ijc.21478 · DOI
  80. Citrin, 2009, In vitro and in vivo radiosensitization with AZD6244 (ARRY-142886), an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 kinase, Clin Cancer Res, 15, 3050, 10.1158/1078-0432.CCR-08-2954 · DOI
  81. Hallahan, 2002, Phosphatidylinositol 3-kinase/Akt signaling in the response to vascular endothelium to ionizing radiation, Cancer Res, 62, 4671
  82. Lu, 2005, Enhanced radiation damage of tumor vasculature by mTOR inhibitors, Oncogene, 24, 5414, 10.1038/sj.onc.1208715 · DOI
  83. Yahalom, 2005, Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells, Cancer Res, 65, 11061, 10.1158/0008-5472.CAN-05-1083 · DOI
  84. Lu, 2007, Crosstalk between Bak/Bax and mTOR signaling regulates radiation induced autophagy, Autophagy, 3, 142, 10.4161/auto.3607 · DOI
  85. Martelli, 2009, Targeting the leukemic stem cell—the holy grail of leukemia therapy, Leukemia, 23, 25, 10.1038/leu.2008.246 · DOI
  86. Haber, 2008, Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma, Cancer Res, 68, 4853, 10.1158/0008-5472.CAN-07-6787 · DOI
  87. Flaherty, 2008, Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas, Mol Cancer Ther, 7, 2876, 10.1158/1535-7163.MCT-08-0431 · DOI
  88. Shirasawa, 2010, Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus, J Clin Invest, 120, 2858, 10.1172/JCI37539 · DOI
  89. Park, 2010, PIK3CA and KRAS mutations predict for response to everolimus therapy: now that's RAD001, J Clin Invest, 120, 2
  90. Shokat, 2008, Discovery of drug-resistant and drug-sensitizing mutations in the oncogenic PI3K isoform p110α, Cancer Cell, 14, 180, 10.1016/j.ccr.2008.06.014 · DOI
  91. Cheng, 2008, Micro RNA expression profiling in human ovarian cancer: miR-274 induces cell survival and cisplatin resistance by targeting PTEN, Cancer Res, 68, 425, 10.1158/0008-5472.CAN-07-2488 · DOI
  92. Fagin, 2006, Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo, Clin Cancer Res, 12, 1785, 10.1158/1078-0432.CCR-05-1729 · DOI
  93. Friedman, 2006, AAL881, a novel small molecule inhibitor of RAF and vascular endothelial growth factor receptor activities, blocks the growth of malignant glioma, Cancer Res, 66, 8722, 10.1158/0008-5472.CAN-06-0284 · DOI
  94. Shen, 2009, A phase I study of XL281, a selective oral RAF kinase inhibitor, in patients (Pts) with advanced solid tumors, J Clin Oncol, 27, 3
  95. Wang, 2006, Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885, Cancer Res, 66, 11100, 10.1158/0008-5472.CAN-06-2554 · DOI
  96. Lenormand, 2009, Total ERK1/2 activity regulates cell proliferation, Cell Cycle, 8, 705, 10.4161/cc.8.5.7734 · DOI
  97. Koromilas, 2009, Stat1 is an inhibitor of Ras-MAPK signaling and Rho small GTPase expression with implications in the transcriptional signature of Ras transformed cells, Cell Cycle, 8, 2070, 10.4161/cc.8.13.8891 · DOI
  98. Saltiel, 1995, A synthetic inhibitor of the mitogen-activated protein kinase cascade, Proc Natl Acad Sci USA, 92, 7686, 10.1073/pnas.92.17.7686 · DOI
  99. Guadagon, 2008, Knockdown of B-Raf impairs spindle formation and the mitotic checkpoint in human somatic cells, Cell Cycle, 7, 2894, 10.4161/cc.7.18.6678 · DOI
  100. Magolda, 1998, Identification of a novel inhibitor of mitogen-activated protein kinase kinase, J Biol Chem, 273, 18623, 10.1074/jbc.273.29.18623 · DOI
  101. Kluger, 2009, C-Raf is associated with disease progression and cell proliferation in a subset of melanomas, Clin Cancer Res., 5, 5704
  102. Reith, 2008, The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase, Bioorg Med Chem Lett, 18, 4373, 10.1016/j.bmcl.2008.06.070 · DOI
  103. Brown, 1994, A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), J Biol Chem, 269, 5241, 10.1016/S0021-9258(17)37680-9 · DOI
  104. Plunkett, 2006, Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial, Blood, 107, 2517, 10.1182/blood-2005-08-3351 · DOI
  105. Knudsen, 2008, RB status governs differential sensitivity to cytotoxic and molecularly-targeted therapeutic agents, Cell Cycle, 7, 1095, 10.4161/cc.7.8.5737 · DOI
  106. Martelli, 2008, Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells, Leukemia, 22, 147, 10.1038/sj.leu.2404980 · DOI
  107. García-Echeverría, 2008, Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway, Bioorg Med Chem Lett, 18, 1027, 10.1016/j.bmcl.2007.12.018 · DOI
  108. Galinsky, 2008, Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells, Blood, 111, 3723, 10.1182/blood-2007-09-114454 · DOI
  109. Geske, 2008, Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity, Cancer Res, 68, 2366, 10.1158/0008-5472.CAN-07-5783 · DOI
  110. Kumar, 2009, AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines, Blood, 113, 1723, 10.1182/blood-2008-02-137737 · DOI
  111. Houghton, 2001, Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition, Clin Cancer Res, 7, 1758
  112. Konopleva, 2007, Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML, Blood, 109, 3509, 10.1182/blood-2006-06-030833 · DOI
  113. Pandolfi, 2008, Deconstructing feedback-signaling networks to improve anticancer therapy with mTORC1 inhibitors, Cell Cycle, 7, 3805, 10.4161/cc.7.24.7244 · DOI
  114. Andreeff, 2006, Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies, Clin Cancer Res, 12, 5165, 10.1158/1078-0432.CCR-06-0764 · DOI
  115. Giles, 2008, A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies, Clin Cancer Res, 14, 2756, 10.1158/1078-0432.CCR-07-1372 · DOI
  116. Elit, 2006, Drug evaluation: AP-23573--an mTOR inhibitor for the treatment of cancer, IDrugs., 9, 636
  117. Wouters, 2001, Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro, Cancer Res, 61, 131
  118. Adjei, 2002, Farnesyltransferase inhibitors in breast cancer therapy, Cancer Invest, 20, 30, 10.1081/CNV-120014884 · DOI
  119. Yean, 2010, SR16388: a steroidal antiangiogenic agent with potent inhibitory effect on tumor growth in vivo, Angiogenesis.
  120. Lentz, 2005, Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1, J Biol Chem, 280, 19867, 10.1074/jbc.M501367200 · DOI
  121. Alessi, 2008, Small-molecule inhibitors of PDK1, ChemMedChem., 3, 1810, 10.1002/cmdc.200800195 · DOI
  122. Cohen, 2007, The selectivity of protein kinase inhibitors: a further update, Biochem J, 408, 297, 10.1042/BJ20070797 · DOI
  123. Weiss, 2006, A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling, Cell, 125, 733, 10.1016/j.cell.2006.03.035 · DOI · Paper page
  124. Weiss, 2006, A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma, Cancer Cell, 9, 341, 10.1016/j.ccr.2006.03.029 · DOI
  125. Bernhard, 2008, Class I PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103 enhances tumor radiosensitivity, Cancer Res, 68, 5915, 10.1158/0008-5472.CAN-08-0757 · DOI
  126. Li, 2009, A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells, Int J Mol Med, 24, 97, 10.3892/ijmm_00000212 · DOI
  127. Dent, 2006, OSU-03012 promotes caspase-independent but PERK-, cathepsin B-, BID-, and AIF-dependent killing of transformed cells, Mol Pharmacol, 70, 589, 10.1124/mol.106.025007 · DOI
  128. Chen, 2008, Sensitizing estrogen receptor-negative breast cancer cells to tamoxifen with OSU-03012, a novel celecoxib-derived phosphoinositide-dependent protein kinase-1/Akt signaling inhibitor, Mol Cancer Ther, 7, 800, 10.1158/1535-7163.MCT-07-0434 · DOI
  129. Cheng, 2008, OSU-03012, a novel celecoxib derivative, induces reactive oxygen species-related autophagy in hepatocellular carcinoma, Cancer Res, 68, 9348, 10.1158/0008-5472.CAN-08-1642 · DOI
  130. Powis, 2004, Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling, Mol Cancer Ther, 3, 763, 10.1158/1535-7163.763.3.7 · DOI
  131. Abraham, 2007, The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures, Mol Cancer Ther, 6, 2505, 10.1158/1535-7163.MCT-06-0698 · DOI
  132. Petersen, 2005, PWT-458, a novel pegylated-17-hydroxywortmannin, inhibits phosphatidylinositol 3-kinase signaling and suppresses growth of solid tumors, Cancer Biol Ther, 4, 538, 10.4161/cbt.4.5.1660 · DOI
  133. Fawzi, 2006, Pegylated wortmannin and 17-hydroxywortmannin conjugates as phosphoinositide 3-kinase inhibitors active in human tumor xenograft models, J Med Chem, 49, 1373, 10.1021/jm050901o · DOI
  134. Williams, 2000, Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine, Mol Cell, 6, 909, 10.1016/S1097-2765(05)00089-4 · DOI
  135. Stein, 2001, Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment, Endocr Relat Cancer, 8, 237, 10.1677/erc.0.0080237 · DOI
  136. Lu, 2006, Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia, Cancer Res, 66, 3737, 10.1158/0008-5472.CAN-05-1278 · DOI
  137. Yung, 2006, Inhibition of Akt survival pathway by a small-molecule inhibitor in human glioblastoma, Mol Cancer Ther, 5, 637, 10.1158/1535-7163.MCT-05-0453 · DOI
  138. Baselga, 2009, Phase I dose-escalation study of XL147, a PI3K inhibitor administered orally to patients with solid tumors, J Clin Oncol, 27, 3
  139. Yamori, 2006, Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor, J Natl Cancer Inst, 98, 545, 10.1093/jnci/djj133 · DOI
  140. Yamori, 2009, Antiangiogenic effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, Eur J Cancer, 45, 857, 10.1016/j.ejca.2008.12.007 · DOI
  141. Siu, 2008, First-in-class, first-in-human phase I results of targeted agents: Highlights of the 2008 American Society of Clinical Oncology meeting, J Hematol Oncol, 1, 20, 10.1186/1756-8722-1-20 · DOI
  142. Hayes, 2008, The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer, J Med Chem, 51, 5522, 10.1021/jm800295d · DOI
  143. Henley, 2009, Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941, Mol Cancer Ther, 8, 1725, 10.1158/1535-7163.MCT-08-1200 · DOI
  144. Sliwkowski, 2009, Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab, Clin Cancer Res, 15, 4147, 10.1158/1078-0432.CCR-08-2814 · DOI
  145. Garcia-Echeverria, 2008, NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations, Cancer Res, 68, 8022, 10.1158/0008-5472.CAN-08-1385 · DOI · Paper page
  146. Yung, 2009, NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas, Mol Cancer Ther, 8, 2204, 10.1158/1535-7163.MCT-09-0160 · DOI
  147. Lin, 2008, Rapamycin and mTOR kinase inhibitors, J Chem Biol, 1, 27, 10.1007/s12154-008-0003-5 · DOI
  148. Brown, 2009, Mammalian target of rapamycin inhibitors and their potential role in therapy in leukaemia and other haematological malignancies, Br J Haematol, 145, 569, 10.1111/j.1365-2141.2009.07657.x · DOI
  149. Wymann, 2009, Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors, Mol Cancer Res, 7, 601, 10.1158/1541-7786.MCR-08-0366 · DOI
  150. Françon, 2006, Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma, J Med Chem, 49, 3857, 10.1021/jm0601598 · DOI
  151. Steadman, 2006, The identification of potent and selective imidazole-based inhibitors of B-Raf kinase, Bioorg Med Chem Lett, 16, 378, 10.1016/j.bmcl.2005.09.072 · DOI
  152. Bally, 2006, Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells, Mol Cancer Ther, 5, 645, 10.1158/1535-7163.MCT-05-0099 · DOI
  153. Rich, 2007, The combination of novel low molecular weight inhibitors of RAF (LBT613) and target of rapamycin (RAD001) decreases glioma proliferation and invasion, Mol Cancer Ther, 6, 2449, 10.1158/1535-7163.MCT-07-0155 · DOI
  154. Strumberg, 2003, Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006, Int J Clin Pharmacol Ther, 41, 616, 10.5414/CPP41616 · DOI
  155. Feuerstein, 2003, Significant neuroprotection against ischemic brain injury by inhibition of the MEK1 protein kinase in mice: exploration of potential mechanism associated with apoptosis, J Pharmacol Exp Ther, 304, 172, 10.1124/jpet.102.040246 · DOI
  156. Wright, 2008, Advantages of a selective beta-isoform phosphoinositide 3-kinase antagonist, an anti-thrombotic agent devoid of other cardiovascular actions in the rat, Eur J Pharmacol, 587, 209, 10.1016/j.ejphar.2008.03.017 · DOI
  157. Yamori, 2009, Advances in development of phosphatidylinositol 3-kinase inhibitors, Curr Med Chem, 16, 2839, 10.2174/092986709788803222 · DOI
  158. Ogier-Denis, 2002, Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line, J Biol Chem, 277, 27613, 10.1074/jbc.M201119200 · DOI
  159. Chen, 2004, 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells, Cancer Res, 64, 1444, 10.1158/0008-5472.CAN-03-2396 · DOI
  160. Li, 2005, Optimal classes of chemotherapeutic agents sensitized by specific small-molecule inhibitors of akt in vitro and in vivo, Neoplasia, 7, 992, 10.1593/neo.05355 · DOI
  161. Pledger, 2009, Apoptosis of metastatic prostate cancer cells by a combination of cyclin-dependent kinase and AKT inhibitors, Int J Biochem Cell Biol, 41, 595, 10.1016/j.biocel.2008.07.013 · DOI
  162. McCubrey, 2010, Preclinical testing of the Akt inhibitor triciribine in T-cell acute lymphoblastic leukemia, J of Cellular Physiology, 226, 822
  163. Martelli, 2010, Identification of a functional nuclear export sequence in diacyl glycerol kinase delta, Cell Cycle, 9, 384, 10.4161/cc.9.2.10469 · DOI
  164. Basecke, 2010, Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK2- and PP2-dependent mechanisms, Leukemia, 24, 687, 10.1038/leu.2010.32 · DOI
  165. Martelli, 2009, The cyclin-dependent kinase inhibitor Roscovitine and the nucleoside analog sangivamycin induce apoptosis in caspase-3 deficient breast cancer cells independent of caspase mediated P-glycoprotein cleavage: Implications for therapy of drug resistant breast cancers, Cell Cycle, 8, 1421, 10.4161/cc.8.9.8323 · DOI
  166. McCubrey, 2010, Activity of the novel dual phosphatidylinositol 3-kinasse/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia, Cancer Res, 70, 8097, 10.1158/0008-5472.CAN-10-1814 · DOI
  167. Martelli, 2011, Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell aculte lymphoblastic leukemia, Leukemia
  168. McCubrey, 2010, The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients, Oncotarget, 1, 89, 10.18632/oncotarget.114 · DOI
  169. Coffer, 2009, The role of the PI3K-PKB signaling module in regulation of hematopoiesis, Cell Cycle, 8, 560, 10.4161/cc.8.4.7654 · DOI
  170. McCubrey, 2010, The emerging role of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in cancer stem cell biology, Cancers, 2, 1576, 10.3390/cancers2031576 · DOI
  171. McCubrey, 2010, The emerging role of the phosphatiylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in normal myelopoiesis and leukemogensis, Biochim Biophys Act, 1803, 991, 10.1016/j.bbamcr.2010.04.005 · DOI
  172. Yu, 2009, Targeting mTOR globally in cancer: thinking beyond rapamycin, Cell Cycle., 8, 3831, 10.4161/cc.8.23.10070 · DOI
  173. Taketo, 2009, The role of mTORC1 pathway in intestinal tumorigenesis, Cell Cycle, 8, 3684, 10.4161/cc.8.22.9946 · DOI
  174. Blenis, 2009, Not all substrates are treated equally: implications for mTOR, rapamycin-resistance and cancer therapy, Cell Cycle, 8, 567, 10.4161/cc.8.4.7659 · DOI
  175. DePinho, 2009, mTORC1 signaling governs hematopoietic stem cell quiescence, Cell Cycle, 8, 1003, 10.4161/cc.8.7.8045 · DOI
  176. Zamoyska, 2010, How does the mammalian target of rapamycin (mTOR) influence CD8 T cell differentiation?, Cell Cycle, 9, 2952
  177. Shrikant, 2010, Fine-tuning CD8(+) T cell functional responses: mTOR acts as a rheostat for regulating CD8(+) T cell proliferation, survival and differentiation?, Cell Cycle, 9, 2996
  178. Manenti, 2010, A functional link between polo-like kinase 1 and the mammalian target-of-rapamycin pathway?, Cell Cycle, 9, 1690, 10.4161/cc.9.9.11295 · DOI
  179. Zheng, 2010, mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes, Cell Cycle, 9, 953, 10.4161/cc.9.5.10876 · DOI
  180. Guan, 2009, RAG GTPases in nutrient-mediated TOR signaling pathway, Cell Cycle, 8, 1014, 10.4161/cc.8.7.8124 · DOI
  181. Morrison, 2006, PTEN-dependence distinguishes haematopoietic stem cells from leukemia-initating cells, Nature, 441, 475, 10.1038/nature04703 · DOI · Paper page
  182. Blagosklonny, 2007, Cancer stem cell and cancer stemloids: from biology to therapy, Cancer Biology & Therapy, 6, 1684, 10.4161/cbt.6.11.5167 · DOI
  183. Libra, 2009, PIK3CA mutations in human solid tumors, Cell Cycle, 8, 1352, 10.4161/cc.8.9.8255 · DOI · Paper page
  184. Hosokawa, 2007, Foxo3a is essential for maintenance of the hematopoietic stem cell pool, Cell Stem Cell, 1, 101, 10.1016/j.stem.2007.02.001 · DOI · Paper page
  185. Pandolfi, 2008, PML targeting eradicates quiescent leukaemia-initiating cells, Nature, 453, 1072, 10.1038/nature07016 · DOI
  186. Pandolfi, 2009, A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell, Genes Devel, 19, 51
  187. Steelman, 2010, Targeting signal transduction pathways to eliminate chemotherapeutic drug resistance and cancer stem cells, Advan in Enzy Regul, 50, 285, 10.1016/j.advenzreg.2009.10.016 · DOI
  188. Steelman, 2011, Targeting the cancer initiating cells: the Achilles' heel of cancer, Adv Enzyme Regul, 51
  189. Chen, 2009, Evaluation of radiotherapy effect in resveratrol-treated medulloblastoma cancer stem-like cells, Childs Nerv Syst., 25, 543, 10.1007/s00381-009-0826-6 · DOI
  190. Srivastava, 2011, Resveratrol inhibits pancreatic cancer stem cell characteristics in human and kras transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition, PLoS One., 6, e16530, 10.1371/journal.pone.0016530 · DOI
  191. Libra, 2009, The involvement of the transcription factor yin yang 1 in cancer development and progression, Cell Cycle, 8, 1367, 10.4161/cc.8.9.8314 · DOI
  192. Laidler, 2011, The mechanism of contribution of integrin linked kinase (ILK) to epithelial mesenchymal transition, Adv Enzyme Regul, 51
  193. Morrison, 2010, mTOR Activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion, Cell Stem Cell, 7, 593, 10.1016/j.stem.2010.09.015 · DOI
  194. Guan, 2008, CD133+ cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway, Oncogene, 27, 1749, 10.1038/sj.onc.1210811 · DOI
  195. Graves, 2010, Lyn kinase-dependent regulation of miR181 and myeloid cell leukemia-1 expression: implications for drug resistance in myelogenous leukemia, Mol Pharmacol, 78, 811, 10.1124/mol.110.066258 · DOI
  196. Holland, 2008, PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo, Genes Dev, 22, 436, 10.1101/gad.1627008 · DOI
  197. Holland, 2010, The perivascular niche microenvironment in brain tumor progression, Cell Cycle, 9, 3012
  198. Humphries, 2010, Biologic and experimental variation of measured cancer stem cells, Cell Cycle, 9, 909, 10.4161/cc.9.5.10852 · DOI
  199. Dean, 2010, Tumor initiation via loss of cell contact inhibition versus Ras mutation: do all roads lead to EMT?, Cell Cycle, 9, 897, 10.4161/cc.9.5.10933 · DOI
  200. du Manoir, 2010, An adult tissue-specific stem cell molecular phenotype is activated in epithelial cancer stem cells and correlated to patient outcome, Cell Cycle, 9, 321, 10.4161/cc.9.2.10421 · DOI

200 of 261 shown

Cited by

Sorted by citations

Metadata

Authors
Chappell, W. H., Steelman, L. S., Long, J. M., Kempf, R. C., Abrams, S. L., Franklin, R. A., Bäsecke, J., Stivala, F., Donia, M., Fagone, P., Malaponte, G., Mazzarino, M. C., Nicoletti, F., Libra, M., Maksimovic-Ivanic, D., Mijatovic, S., Montalto, G., Cervello, M., Laidler, P., Milella, M., Tafuri, A., Bonati, A., Evangelisti, C., Cocco, L., Martelli, A. M., & McCubrey, J. A.
Affiliations
  • Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University
  • Department of Physics, Greenville, NC 27858 USA
  • Department of Medicine University of Göttingen, Göttingen, Germany
  • Department of Biomedical Sciences, University of Catania, Catania, Italy
  • Department of Immunology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia
  • Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy
  • Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy
  • Department of Medical Biochemistry Jagiellonian University Medical College, Krakow, Poland
  • Regina Elena Cancer Center, Via Elio Chianesi n.53, Rome 00144, Italy
  • University of Rome, La Sapienza, Department of Hematology-Oncology, Via Benevento 6, Rome 99161, Italy
  • University Hospital of Parma, Unit of Hematology and Bone-Marrow Transplantation, Via Gramsi n.14, Parma 43100, Italy
  • Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Università di Bologna, Bologna, Italy
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2011-03-11
Volume
2
Issue
3
Pages
135-164
ISSN
1949-2553
DOI
10.18632/oncotarget.240
PMC
PMC3260807
Cited by
510
References
12
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review