1,243
Views
1
CrossRef citations to date
0
Altmetric
Review

Targeting translation initiation in breast cancer

, &
Article: e28968 | Received 07 Jan 2014, Accepted 22 Apr 2014, Published online: 29 Apr 2014

References

  • American Cancer Society. Cancer Facts and Figures 2013. Atlanta, GA: American Cancer Society, 2013.
  • Meric F, Hunt KK. Translation initiation in cancer: a novel target for therapy. Mol Cancer Ther 2002; 1:971 - 9; PMID: 12481419
  • Silvera D, Formenti SC, Schneider RJ. Translational control in cancer. Nat Rev Cancer 2010; 10:254 - 66; http://dx.doi.org/10.1038/nrc2824; PMID: 20332778
  • Grzmil M, Hemmings BA. Translation regulation as a therapeutic target in cancer. Cancer Res 2012; 72:3891 - 900; http://dx.doi.org/10.1158/0008-5472.CAN-12-0026; PMID: 22850420
  • Malina A, Cencic R, Pelletier J. Targeting translation dependence in cancer. Oncotarget 2011; 2:76 - 88; PMID: 21378410
  • Ruggero D. Translational control in cancer etiology. Cold Spring Harb Perspect Biol 2013; 5:5; http://dx.doi.org/10.1101/cshperspect.a012336; PMID: 22767671
  • Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 2009; 136:731 - 45; http://dx.doi.org/10.1016/j.cell.2009.01.042; PMID: 19239892
  • Gingras AC, Raught B, Sonenberg N. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem 1999; 68:913 - 63; http://dx.doi.org/10.1146/annurev.biochem.68.1.913; PMID: 10872469
  • Blagden SP, Willis AE. The biological and therapeutic relevance of mRNA translation in cancer. Nat Rev Clin Oncol 2011; 8:280 - 91; http://dx.doi.org/10.1038/nrclinonc.2011.16; PMID: 21364523
  • Aitken CE, Lorsch JR. A mechanistic overview of translation initiation in eukaryotes. Nat Struct Mol Biol 2012; 19:568 - 76; http://dx.doi.org/10.1038/nsmb.2303; PMID: 22664984
  • Wells SE, Hillner PE, Vale RD, Sachs AB. Circularization of mRNA by eukaryotic translation initiation factors. Mol Cell 1998; 2:135 - 40; http://dx.doi.org/10.1016/S1097-2765(00)80122-7; PMID: 9702200
  • Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009; 27:2278 - 87; http://dx.doi.org/10.1200/JCO.2008.20.0766; PMID: 19332717
  • Hsieh AC, Truitt ML, Ruggero D. Oncogenic AKTivation of translation as a therapeutic target. Br J Cancer 2011; 105:329 - 36; http://dx.doi.org/10.1038/bjc.2011.241; PMID: 21772331
  • Meric-Bernstam F. Translation initiation factor 4E (eIF4E): prognostic marker and potential therapeutic target. Ann Surg Oncol 2008; 15:2996 - 7; http://dx.doi.org/10.1245/s10434-008-0116-7; PMID: 18712446
  • Li BD, McDonald JC, Nassar R, De Benedetti A. Clinical outcome in stage I to III breast carcinoma and eIF4E overexpression. Ann Surg 1998; 227:756-6l; discussion 61-3.
  • Dever TE, Green R. The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb Perspect Biol 2012; 4:a013706; http://dx.doi.org/10.1101/cshperspect.a013706; PMID: 22751155
  • Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 2006; 314:467 - 71; http://dx.doi.org/10.1126/science.1130276; PMID: 17053147
  • Wang X, Li W, Williams M, Terada N, Alessi DR, Proud CG. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J 2001; 20:4370 - 9; http://dx.doi.org/10.1093/emboj/20.16.4370; PMID: 11500364
  • Ferrari S, Bandi HR, Hofsteenge J, Bussian BM, Thomas G. Mitogen-activated 70K S6 kinase. Identification of in vitro 40 S ribosomal S6 phosphorylation sites. J Biol Chem 1991; 266:22770 - 5; PMID: 1939282
  • Yamnik RL, Holz MK. mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation. FEBS Lett 2010; 584:124 - 8; http://dx.doi.org/10.1016/j.febslet.2009.11.041; PMID: 19925796
  • Holcik M, Sonenberg N, Korneluk RG. Internal ribosome initiation of translation and the control of cell death. Trends Genet 2000; 16:469 - 73; http://dx.doi.org/10.1016/S0168-9525(00)02106-5; PMID: 11050335
  • Sherrill KW, Byrd MP, Van Eden ME, Lloyd RE. BCL-2 translation is mediated via internal ribosome entry during cell stress. J Biol Chem 2004; 279:29066 - 74; http://dx.doi.org/10.1074/jbc.M402727200; PMID: 15123638
  • Notari M, Neviani P, Santhanam R, Blaser BW, Chang JS, Galietta A, Willis AE, Roy DC, Caligiuri MA, Marcucci G, et al. A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation. Blood 2006; 107:2507 - 16; http://dx.doi.org/10.1182/blood-2005-09-3732; PMID: 16293596
  • Lang KJ, Kappel A, Goodall GJ. Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia. Mol Biol Cell 2002; 13:1792 - 801; http://dx.doi.org/10.1091/mbc.02-02-0017; PMID: 12006670
  • Miller DL, Dibbens JA, Damert A, Risau W, Vadas MA, Goodall GJ. The vascular endothelial growth factor mRNA contains an internal ribosome entry site. FEBS Lett 1998; 434:417 - 20; http://dx.doi.org/10.1016/S0014-5793(98)01025-4; PMID: 9742966
  • Holcik M, Yeh C, Korneluk RG, Chow T. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene 2000; 19:4174 - 7; http://dx.doi.org/10.1038/sj.onc.1203765; PMID: 10962579
  • Meric-Bernstam F, Chen H, Akcakanat A, Do KA, Lluch A, Hennessy BT, Hortobagyi GN, Mills GB, Gonzalez-Angulo AM. Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer. Breast Cancer Res 2012; 14:R138; http://dx.doi.org/10.1186/bcr3343; PMID: 23102376
  • Miller TW, Hennessy BT, González-Angulo AM, Fox EM, Mills GB, Chen H, Higham C, García-Echeverría C, Shyr Y, Arteaga CL. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest 2010; 120:2406 - 13; http://dx.doi.org/10.1172/JCI41680; PMID: 20530877
  • Zhang L, Pan X, Hershey JW. Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells. J Biol Chem 2007; 282:5790 - 800; http://dx.doi.org/10.1074/jbc.M606284200; PMID: 17170115
  • Bachmann F, Bänziger R, Burger MM. Cloning of a novel protein overexpressed in human mammary carcinoma. Cancer Res 1997; 57:988 - 94; PMID: 9041205
  • Yin JY, Shen J, Dong ZZ, Huang Q, Zhong MZ, Feng DY, Zhou HH, Zhang JT, Liu ZQ. Effect of eIF3a on response of lung cancer patients to platinum-based chemotherapy by regulating DNA repair. Clin Cancer Res 2011; 17:4600 - 9; http://dx.doi.org/10.1158/1078-0432.CCR-10-2591; PMID: 21610145
  • Dong Z, Zhang JT. EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression. Mol Biol Cell 2003; 14:3942 - 51; http://dx.doi.org/10.1091/mbc.E02-12-0784; PMID: 12972576
  • Dong Z, Liu LH, Han B, Pincheira R, Zhang JT. Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth. Oncogene 2004; 23:3790 - 801; http://dx.doi.org/10.1038/sj.onc.1207465; PMID: 15094776
  • Rothe M, Ko Y, Albers P, Wernert N. Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas. Am J Pathol 2000; 157:1597 - 604; http://dx.doi.org/10.1016/S0002-9440(10)64797-9; PMID: 11073819
  • Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst SM. Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c). Hum Mol Genet 2006; 15:1059 - 70; http://dx.doi.org/10.1093/hmg/ddl021; PMID: 16497727
  • Nupponen NN, Porkka K, Kakkola L, Tanner M, Persson K, Borg A, Isola J, Visakorpi T. Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer. Am J Pathol 1999; 154:1777 - 83; http://dx.doi.org/10.1016/S0002-9440(10)65433-8; PMID: 10362802
  • Shi J, Kahle A, Hershey JW, Honchak BM, Warneke JA, Leong SP, Nelson MA. Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells. Oncogene 2006; 25:4923 - 36; http://dx.doi.org/10.1038/sj.onc.1209495; PMID: 16532022
  • LeFebvre AK, Korneeva NL, Trutschl M, Cvek U, Duzan RD, Bradley CA, Hershey JW, Rhoads RE. Translation initiation factor eIF4G-1 binds to eIF3 through the eIF3e subunit. J Biol Chem 2006; 281:22917 - 32; http://dx.doi.org/10.1074/jbc.M605418200; PMID: 16766523
  • Rasmussen SB, Kordon E, Callahan R, Smith GH. Evidence for the transforming activity of a truncated Int6 gene, in vitro. Oncogene 2001; 20:5291 - 301; http://dx.doi.org/10.1038/sj.onc.1204624; PMID: 11536042
  • Marchetti A, Buttitta F, Pellegrini S, Bertacca G, Callahan R. Reduced expression of INT-6/eIF3-p48 in human tumors. Int J Oncol 2001; 18:175 - 9; PMID: 11115556
  • Umar A, Kang H, Timmermans AM, Look MP, Meijer-van Gelder ME, den Bakker MA, Jaitly N, Martens JW, Luider TM, Foekens JA, et al. Identification of a putative protein profile associated with tamoxifen therapy resistance in breast cancer. Mol Cell Proteomics 2009; 8:1278 - 94; http://dx.doi.org/10.1074/mcp.M800493-MCP200; PMID: 19329653
  • Gillis LD, Lewis SM. Decreased eIF3e/Int6 expression causes epithelial-to-mesenchymal transition in breast epithelial cells. Oncogene 2013; 32:3598 - 605; http://dx.doi.org/10.1038/onc.2012.371; PMID: 22907435
  • Bandyopadhyay A, Matsumoto T, Maitra U. Fission yeast Int6 is not essential for global translation initiation, but deletion of int6(+) causes hypersensitivity to caffeine and affects spore formation. Mol Biol Cell 2000; 11:4005 - 18; http://dx.doi.org/10.1091/mbc.11.11.4005; PMID: 11071923
  • Grzmil M, Rzymski T, Milani M, Harris AL, Capper RG, Saunders NJ, Salhan A, Ragoussis J, Norbury CJ. An oncogenic role of eIF3e/INT6 in human breast cancer. Oncogene 2010; 29:4080 - 9; http://dx.doi.org/10.1038/onc.2010.152; PMID: 20453879
  • Rozen F, Edery I, Meerovitch K, Dever TE, Merrick WC, Sonenberg N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol Cell Biol 1990; 10:1134 - 44; PMID: 2304461
  • Shuda M, Kondoh N, Tanaka K, Ryo A, Wakatsuki T, Hada A, Goseki N, Igari T, Hatsuse K, Aihara T, et al. Enhanced expression of translation factor mRNAs in hepatocellular carcinoma. Anticancer Res 2000; 20:2489 - 94; PMID: 10953316
  • Eberle J, Krasagakis K, Orfanos CE. Translation initiation factor eIF-4A1 mRNA is consistently overexpressed in human melanoma cells in vitro. Int J Cancer 1997; 71:396 - 401; http://dx.doi.org/10.1002/(SICI)1097-0215(19970502)71:3<396::AID-IJC16>3.0.CO;2-E; PMID: 9139875
  • Schroeder JA, Masri AA, Adriance MC, Tessier JC, Kotlarczyk KL, Thompson MC, Gendler SJ. MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. Oncogene 2004; 23:5739 - 47; http://dx.doi.org/10.1038/sj.onc.1207713; PMID: 15221004
  • Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 2009; 9:874 - 85; http://dx.doi.org/10.1038/nrc2761; PMID: 19935676
  • Jin C, Rajabi H, Rodrigo CM, Porco JA Jr., Kufe D. Targeting the eIF4A RNA helicase blocks translation of the MUC1-C oncoprotein. Oncogene 2013; 32:2179 - 88; http://dx.doi.org/10.1038/onc.2012.236; PMID: 22689062
  • Bordeleau ME, Robert F, Gerard B, Lindqvist L, Chen SM, Wendel HG, Brem B, Greger H, Lowe SW, Porco JA Jr., et al. Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model. J Clin Invest 2008; 118:2651 - 60; PMID: 18551192
  • Lucas DM, Edwards RB, Lozanski G, West DA, Shin JD, Vargo MA, Davis ME, Rozewski DM, Johnson AJ, Su BN, et al. The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo. Blood 2009; 113:4656 - 66; http://dx.doi.org/10.1182/blood-2008-09-175430; PMID: 19190247
  • Schatz JH, Oricchio E, Wolfe AL, Jiang M, Linkov I, Maragulia J, Shi W, Zhang Z, Rajasekhar VK, Pagano NC, et al. Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma. J Exp Med 2011; 208:1799 - 807; http://dx.doi.org/10.1084/jem.20110846; PMID: 21859846
  • Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA. Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol 1999; 19:1871 - 80; PMID: 10022874
  • Joshi B, Cai AL, Keiper BD, Minich WB, Mendez R, Beach CM, Stepinski J, Stolarski R, Darzynkiewicz E, Rhoads RE. Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. J Biol Chem 1995; 270:14597 - 603; http://dx.doi.org/10.1074/jbc.270.24.14597; PMID: 7782323
  • Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman DM, Manivel JC, Sonenberg N, Yee D, Bitterman PB, et al. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell 2004; 5:553 - 63; http://dx.doi.org/10.1016/j.ccr.2004.05.024; PMID: 15193258
  • De Benedetti A, Graff JR. eIF-4E expression and its role in malignancies and metastases. Oncogene 2004; 23:3189 - 99; http://dx.doi.org/10.1038/sj.onc.1207545; PMID: 15094768
  • Zimmer SG, DeBenedetti A, Graff JR. Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a central regulator of tumor formation, growth, invasion and metastasis. Anticancer Res 2000; 20:3A 1343 - 51; PMID: 10928042
  • Culjkovic B, Tan K, Orolicki S, Amri A, Meloche S, Borden KL. The eIF4E RNA regulon promotes the Akt signaling pathway. J Cell Biol 2008; 181:51 - 63; http://dx.doi.org/10.1083/jcb.200707018; PMID: 18391071
  • Li S, Takasu T, Perlman DM, Peterson MS, Burrichter D, Avdulov S, Bitterman PB, Polunovsky VA. Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release. J Biol Chem 2003; 278:3015 - 22; http://dx.doi.org/10.1074/jbc.M208821200; PMID: 12441348
  • Rhoads RE. Regulation of eukaryotic protein synthesis by initiation factors. J Biol Chem 1993; 268:3017 - 20; PMID: 8428975
  • Rosenwald IB, Kaspar R, Rousseau D, Gehrke L, Leboulch P, Chen JJ, Schmidt EV, Sonenberg N, London IM. Eukaryotic translation initiation factor 4E regulates expression of cyclin D1 at transcriptional and post-transcriptional levels. J Biol Chem 1995; 270:21176 - 80; http://dx.doi.org/10.1074/jbc.270.36.21176; PMID: 7673150
  • Bitterman PB, Polunovsky VA. Attacking a nexus of the oncogenic circuitry by reversing aberrant eIF4F-mediated translation. Mol Cancer Ther 2012; 11:1051 - 61; http://dx.doi.org/10.1158/1535-7163.MCT-11-0530; PMID: 22572598
  • Feoktistova K, Tuvshintogs E, Do A, Fraser CS. Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity. Proc Natl Acad Sci U S A 2013; 110:13339 - 44; http://dx.doi.org/10.1073/pnas.1303781110; PMID: 23901100
  • Larsson O, Li S, Issaenko OA, Avdulov S, Peterson M, Smith K, Bitterman PB, Polunovsky VA. Eukaryotic translation initiation factor 4E induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors. Cancer Res 2007; 67:6814 - 24; http://dx.doi.org/10.1158/0008-5472.CAN-07-0752; PMID: 17638893
  • Ruggero D, Montanaro L, Ma L, Xu W, Londei P, Cordon-Cardo C, Pandolfi PP. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med 2004; 10:484 - 6; http://dx.doi.org/10.1038/nm1042; PMID: 15098029
  • Zindy P, Bergé Y, Allal B, Filleron T, Pierredon S, Cammas A, Beck S, Mhamdi L, Fan L, Favre G, et al. Formation of the eIF4F translation-initiation complex determines sensitivity to anticancer drugs targeting the EGFR and HER2 receptors. Cancer Res 2011; 71:4068 - 73; http://dx.doi.org/10.1158/0008-5472.CAN-11-0420; PMID: 21498638
  • Li BD, Gruner JS, Abreo F, Johnson LW, Yu H, Nawas S, McDonald JC, DeBenedetti A. Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome. Ann Surg 2002; 235:732 - 8, discussion 738-9; http://dx.doi.org/10.1097/00000658-200205000-00016; PMID: 11981220
  • McClusky DR, Chu Q, Yu H, Debenedetti A, Johnson LW, Meschonat C, Turnage R, McDonald JC, Abreo F, Li BD. A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-positive breast cancer. Ann Surg 2005; 242:584 - 90, discussion 590-2; PMID: 16192819
  • Holm N, Byrnes K, Johnson L, Abreo F, Sehon K, Alley J, Meschonat C, Md QC, Li BD. A Prospective Trial on Initiation Factor 4E (eIF4E) Overexpression and Cancer Recurrence in Node-Negative Breast Cancer. Ann Surg Oncol 2008.
  • Flowers A, Chu QD, Panu L, Meschonat C, Caldito G, Lowery-Nordberg M, Li BD. Eukaryotic initiation factor 4E overexpression in triple-negative breast cancer predicts a worse outcome. Surgery 2009; 146:220 - 6; http://dx.doi.org/10.1016/j.surg.2009.05.010; PMID: 19628077
  • Hiller DJ, Chu Q, Meschonat C, Panu L, Burton G, Li BD. Predictive value of eIF4E reduction after neoadjuvant therapy in breast cancer. J Surg Res 2009; 156:265 - 9; http://dx.doi.org/10.1016/j.jss.2009.03.060; PMID: 19665145
  • Graff JR, Konicek BW, Lynch RL, Dumstorf CA, Dowless MS, McNulty AM, Parsons SH, Brail LH, Colligan BM, Koop JW, et al. eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival. Cancer Res 2009; 69:3866 - 73; http://dx.doi.org/10.1158/0008-5472.CAN-08-3472; PMID: 19383915
  • Coleman LJ, Peter MB, Teall TJ, Brannan RA, Hanby AM, Honarpisheh H, Shaaban AM, Smith L, Speirs V, Verghese ET, et al. Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. Br J Cancer 2009; 100:1393 - 9; http://dx.doi.org/10.1038/sj.bjc.6605044; PMID: 19367274
  • Braunstein S, Karpisheva K, Pola C, Goldberg J, Hochman T, Yee H, Cangiarella J, Arju R, Formenti SC, Schneider RJ. A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Mol Cell 2007; 28:501 - 12; http://dx.doi.org/10.1016/j.molcel.2007.10.019; PMID: 17996713
  • Liu J, Stevens PD, Eshleman NE, Gao T. Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1). J Biol Chem 2013; 288:23225 - 33; http://dx.doi.org/10.1074/jbc.M113.492371; PMID: 23814053
  • Fukuchi-Shimogori T, Ishii I, Kashiwagi K, Mashiba H, Ekimoto H, Igarashi K. Malignant transformation by overproduction of translation initiation factor eIF4G. Cancer Res 1997; 57:5041 - 4; PMID: 9371500
  • Ramírez-Valle F, Braunstein S, Zavadil J, Formenti SC, Schneider RJ. eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy. J Cell Biol 2008; 181:293 - 307; http://dx.doi.org/10.1083/jcb.200710215; PMID: 18426977
  • Silvera D, Arju R, Darvishian F, Levine PH, Zolfaghari L, Goldberg J, Hochman T, Formenti SC, Schneider RJ. Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer. Nat Cell Biol 2009; 11:903 - 8; http://dx.doi.org/10.1038/ncb1900; PMID: 19525934
  • Mahoney SJ, Dempsey JM, Blenis J. Cell signaling in protein synthesis ribosome biogenesis and translation initiation and elongation. Prog Mol Biol Transl Sci 2009; 90:53 - 107; http://dx.doi.org/10.1016/S1877-1173(09)90002-3; PMID: 20374739
  • Wu H, Yang JM, Jin S, Zhang H, Hait WN. Elongation factor-2 kinase regulates autophagy in human glioblastoma cells. Cancer Res 2006; 66:3015 - 23; http://dx.doi.org/10.1158/0008-5472.CAN-05-1554; PMID: 16540650
  • Arora S, Yang JM, Kinzy TG, Utsumi R, Okamoto T, Kitayama T, Ortiz PA, Hait WN. Identification and characterization of an inhibitor of eukaryotic elongation factor 2 kinase against human cancer cell lines. Cancer Res 2003; 63:6894 - 9; PMID: 14583488
  • Alaiya AA, Franzén B, Fujioka K, Moberger B, Schedvins K, Silfversvärd C, Linder S, Auer G. Phenotypic analysis of ovarian carcinoma: polypeptide expression in benign, borderline and malignant tumors. Int J Cancer 1997; 73:678 - 83; http://dx.doi.org/10.1002/(SICI)1097-0215(19971127)73:5<678::AID-IJC11>3.0.CO;2-2; PMID: 9398045
  • Nakamura J, Aoyagi S, Nanchi I, Nakatsuka S, Hirata E, Shibata S, Fukuda M, Yamamoto Y, Fukuda I, Tatsumi N, et al. Overexpression of eukaryotic elongation factor eEF2 in gastrointestinal cancers and its involvement in G2/M progression in the cell cycle. Int J Oncol 2009; 34:1181 - 9; PMID: 19360331
  • Cheng Y, Ren X, Zhang Y, Patel R, Sharma A, Wu H, Robertson GP, Yan L, Rubin E, Yang JM. eEF-2 kinase dictates cross-talk between autophagy and apoptosis induced by Akt Inhibition, thereby modulating cytotoxicity of novel Akt inhibitor MK-2206. Cancer Res 2011; 71:2654 - 63; http://dx.doi.org/10.1158/0008-5472.CAN-10-2889; PMID: 21307130
  • Bagaglio DM, Cheng EH, Gorelick FS, Mitsui K, Nairn AC, Hait WN. Phosphorylation of elongation factor 2 in normal and malignant rat glial cells. Cancer Res 1993; 53:Suppl 2260 - 4; PMID: 8485712
  • Arora S, Yang JM, Hait WN. Identification of the ubiquitin-proteasome pathway in the regulation of the stability of eukaryotic elongation factor-2 kinase. Cancer Res 2005; 65:3806 - 10; http://dx.doi.org/10.1158/0008-5472.CAN-04-4036; PMID: 15867377
  • Cheng EH, Gorelick FS, Czernik AJ, Bagaglio DM, Hait WN. Calmodulin-dependent protein kinases in rat glioblastoma. Cell Growth Differ 1995; 6:615 - 21; PMID: 7647041
  • Parmer TG, Ward MD, Yurkow EJ, Vyas VH, Kearney TJ, Hait WN. Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer. Br J Cancer 1999; 79:59 - 64; http://dx.doi.org/10.1038/sj.bjc.6690012; PMID: 10408694
  • Tekedereli I, Alpay SN, Tavares CD, Cobanoglu ZE, Kaoud TS, Sahin I, Sood AK, Lopez-Berestein G, Dalby KN, Ozpolat B. Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer. PLoS One 2012; 7:e41171; http://dx.doi.org/10.1371/journal.pone.0041171; PMID: 22911754
  • Wen YH, Shi X, Chiriboga L, Matsahashi S, Yee H, Afonja O. Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol Rep 2007; 18:1387 - 93; PMID: 17982621
  • Yang HS, Jansen AP, Nair R, Shibahara K, Verma AK, Cmarik JL, Colburn NH. A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation. Oncogene 2001; 20:669 - 76; http://dx.doi.org/10.1038/sj.onc.1204137; PMID: 11314000
  • Yang HS, Jansen AP, Komar AA, Zheng X, Merrick WC, Costes S, Lockett SJ, Sonenberg N, Colburn NH. The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol 2003; 23:26 - 37; http://dx.doi.org/10.1128/MCB.23.1.26-37.2003; PMID: 12482958
  • Schmid T, Jansen AP, Baker AR, Hegamyer G, Hagan JP, Colburn NH. Translation inhibitor Pdcd4 is targeted for degradation during tumor promotion. Cancer Res 2008; 68:1254 - 60; http://dx.doi.org/10.1158/0008-5472.CAN-07-1719; PMID: 18296647
  • Teske BF, Baird TD, Wek RC. Methods for analyzing eIF2 kinases and translational control in the unfolded protein response. Methods Enzymol 2011; 490:333 - 56; http://dx.doi.org/10.1016/B978-0-12-385114-7.00019-2; PMID: 21266259
  • Backer MV, Backer JM, Chinnaiyan P. Targeting the unfolded protein response in cancer therapy. Methods Enzymol 2011; 491:37 - 56; http://dx.doi.org/10.1016/B978-0-12-385928-0.00003-1; PMID: 21329793
  • Jansson MD, Lund AH. MicroRNA and cancer. Mol Oncol 2012; 6:590 - 610; http://dx.doi.org/10.1016/j.molonc.2012.09.006; PMID: 23102669
  • Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, Bertrand E, Filipowicz W. Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 2005; 309:1573 - 6; http://dx.doi.org/10.1126/science.1115079; PMID: 16081698
  • Kentsis A, Topisirovic I, Culjkovic B, Shao L, Borden KL. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci U S A 2004; 101:18105 - 10; http://dx.doi.org/10.1073/pnas.0406927102; PMID: 15601771
  • Soni A, Akcakanat A, Singh G, Luyimbazi D, Zheng Y, Kim D, Gonzalez-Angulo A, Meric-Bernstam F. eIF4E knockdown decreases breast cancer cell growth without activating Akt signaling. Mol Cancer Ther 2008; 7:1782 - 8; http://dx.doi.org/10.1158/1535-7163.MCT-07-2357; PMID: 18644990
  • Graff JR, Konicek BW, Vincent TM, Lynch RL, Monteith D, Weir SN, Schwier P, Capen A, Goode RL, Dowless MS, et al. Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J Clin Invest 2007; 117:2638 - 48; http://dx.doi.org/10.1172/JCI32044; PMID: 17786246
  • Hong DS, Kurzrock R, Oh Y, Wheler J, Naing A, Brail L, Callies S, André V, Kadam SK, Nasir A, et al. A phase 1 dose escalation, pharmacokinetic, and pharmacodynamic evaluation of eIF-4E antisense oligonucleotide LY2275796 in patients with advanced cancer. Clin Cancer Res 2011; 17:6582 - 91; http://dx.doi.org/10.1158/1078-0432.CCR-11-0430; PMID: 21831956
  • Pharmaceuticals I. Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Carboplatin and Paclitaxel (NSCLC). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2010- [cited 2014 March 27]. Available from: http://clinicaltrials.gov/ct2/show/NCT01234038 NLM identifier: NCT1234038.
  • Pharmaceuticals I. Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Docetaxel and Prednisone (CRPC). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2010- [cited 2014 March 27]. Available from: http://clinicaltrials.gov/ct2/show/NCT01234025 NLM identifier: NCT01234025.
  • Ghosh B, Benyumov AO, Ghosh P, Jia Y, Avdulov S, Dahlberg PS, Peterson M, Smith K, Polunovsky VA, Bitterman PB, et al. Nontoxic chemical interdiction of the epithelial-to-mesenchymal transition by targeting cap-dependent translation. ACS Chem Biol 2009; 4:367 - 77; http://dx.doi.org/10.1021/cb9000475; PMID: 19351181
  • Assouline S, Culjkovic B, Cocolakis E, Rousseau C, Beslu N, Amri A, Caplan S, Leber B, Roy DC, Miller WH Jr., et al. Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): a proof-of-principle clinical trial with ribavirin. Blood 2009; 114:257 - 60; http://dx.doi.org/10.1182/blood-2009-02-205153; PMID: 19433856
  • Borden KL. Targeting the oncogene eIF4E in cancer: From the bench to clinical trials. Clin Invest Med 2011; 34:E315; PMID: 22129918
  • Kraljacic BC, Arguello M, Amri A, Cormack G, Borden K. Inhibition of eIF4E with ribavirin cooperates with common chemotherapies in primary acute myeloid leukemia specimens. Leukemia 2011; 25:1197 - 200; http://dx.doi.org/10.1038/leu.2011.57; PMID: 21455212
  • Jewish General Hospital. A Phase I/II Study of Ribavirin and Low-dose Cytarabine Arabinoside (Ara-C) in Acute Myeloid Leukemia (AML) M4 and M5 Subtypes, and AML With High eIF4E Expression. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2010- [cited 2014 March 27]. Available from: http://clinicaltrials.gov/ct2/show/record/NCT01056523 NLM identifier: NCT01056523.
  • Jewish General Hospital. A Phase I/II Exploratory Study of Ribavirin in Metastatic Breast Cancer Expressing Elevated eIF4E. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2010- [cited 2014 March 27]. Available from: http://clinicaltrials.gov/ct2/show/NCT01056757 NLM identifier: NCT01056757.
  • Westman B, Beeren L, Grudzien E, Stepinski J, Worch R, Zuberek J, Jemielity J, Stolarski R, Darzynkiewicz E, Rhoads RE, et al. The antiviral drug ribavirin does not mimic the 7-methylguanosine moiety of the mRNA cap structure in vitro. RNA 2005; 11:1505 - 13; http://dx.doi.org/10.1261/rna.2132505; PMID: 16131589
  • Yan Y, Svitkin Y, Lee JM, Bisaillon M, Pelletier J. Ribavirin is not a functional mimic of the 7-methyl guanosine mRNA cap. RNA 2005; 11:1238 - 44; http://dx.doi.org/10.1261/rna.2930805; PMID: 16043507
  • Herbert TP, Fåhraeus R, Prescott A, Lane DP, Proud CG. Rapid induction of apoptosis mediated by peptides that bind initiation factor eIF4E. Curr Biol 2000; 10:793 - 6; http://dx.doi.org/10.1016/S0960-9822(00)00567-4; PMID: 10898981
  • Salaün P, Boulben S, Mulner-Lorillon O, Bellé R, Sonenberg N, Morales J, Cormier P. Embryonic-stage-dependent changes in the level of eIF4E-binding proteins during early development of sea urchin embryos. J Cell Sci 2005; 118:1385 - 94; http://dx.doi.org/10.1242/jcs.01716; PMID: 15769855
  • Ko SY, Guo H, Barengo N, Naora H. Inhibition of ovarian cancer growth by a tumor-targeting peptide that binds eukaryotic translation initiation factor 4E. Clin Cancer Res 2009; 15:4336 - 47; http://dx.doi.org/10.1158/1078-0432.CCR-08-2924; PMID: 19458052
  • Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev M, et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 2007; 128:257 - 67; http://dx.doi.org/10.1016/j.cell.2006.11.046; PMID: 17254965
  • Cencic R, Hall DR, Robert F, Du Y, Min J, Li L, Qui M, Lewis I, Kurtkaya S, Dingledine R, et al. Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F. Proc Natl Acad Sci U S A 2011; 108:1046 - 51; http://dx.doi.org/10.1073/pnas.1011477108; PMID: 21191102
  • Bordeleau ME, Matthews J, Wojnar JM, Lindqvist L, Novac O, Jankowsky E, Sonenberg N, Northcote P, Teesdale-Spittle P, Pelletier J. Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation. Proc Natl Acad Sci U S A 2005; 102:10460 - 5; http://dx.doi.org/10.1073/pnas.0504249102; PMID: 16030146
  • Bordeleau ME, Cencic R, Lindqvist L, Oberer M, Northcote P, Wagner G, Pelletier J. RNA-mediated sequestration of the RNA helicase eIF4A by Pateamine A inhibits translation initiation. Chem Biol 2006; 13:1287 - 95; http://dx.doi.org/10.1016/j.chembiol.2006.10.005; PMID: 17185224
  • Kuznetsov G, Xu Q, Rudolph-Owen L, Tendyke K, Liu J, Towle M, Zhao N, Marsh J, Agoulnik S, Twine N, et al. Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A. Mol Cancer Ther 2009; 8:1250 - 60; http://dx.doi.org/10.1158/1535-7163.MCT-08-1026; PMID: 19417157
  • Cencic R, Carrier M, Galicia-Vázquez G, Bordeleau ME, Sukarieh R, Bourdeau A, Brem B, Teodoro JG, Greger H, Tremblay ML, et al. Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol. PLoS One 2009; 4:e5223; http://dx.doi.org/10.1371/journal.pone.0005223; PMID: 19401772
  • Bordeleau ME, Mori A, Oberer M, Lindqvist L, Chard LS, Higa T, Belsham GJ, Wagner G, Tanaka J, Pelletier J. Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A. Nat Chem Biol 2006; 2:213 - 20; http://dx.doi.org/10.1038/nchembio776; PMID: 16532013
  • Tsumuraya T, Ishikawa C, Machijima Y, Nakachi S, Senba M, Tanaka J, Mori N. Effects of hippuristanol, an inhibitor of eIF4A, on adult T-cell leukemia. Biochem Pharmacol 2011; 81:713 - 22; http://dx.doi.org/10.1016/j.bcp.2010.12.025; PMID: 21219881
  • Shi XP, Yin KC, Ahern J, Davis LJ, Stern AM, Waxman L. Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture. Biochim Biophys Acta 1996; 1310:119 - 26; http://dx.doi.org/10.1016/0167-4889(95)00165-4; PMID: 9244184
  • Clement PM, Hanauske-Abel HM, Wolff EC, Kleinman HK, Park MH. The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro. Int J Cancer 2002; 100:491 - 8; http://dx.doi.org/10.1002/ijc.10515; PMID: 12115536
  • Zhou H, Shen T, Luo Y, Liu L, Chen W, Xu B, Han X, Pang J, Rivera CA, Huang S. The antitumor activity of the fungicide ciclopirox. Int J Cancer 2010; 127:2467 - 77; http://dx.doi.org/10.1002/ijc.25255; PMID: 20225320
  • Jasiulionis MG, Luchessi AD, Moreira AG, Souza PP, Suenaga AP, Correa M, Costa CA, Curi R, Costa-Neto CM. Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth. Cell Biochem Funct 2007; 25:109 - 14; http://dx.doi.org/10.1002/cbf.1351; PMID: 16850525
  • Eberhard Y, McDermott SP, Wang X, Gronda M, Venugopal A, Wood TE, Hurren R, Datti A, Batey RA, Wrana J, et al. Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells. Blood 2009; 114:3064 - 73; http://dx.doi.org/10.1182/blood-2009-03-209965; PMID: 19589922
  • Redpath NT, Foulstone EJ, Proud CG. Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J 1996; 15:2291 - 7; PMID: 8641294
  • Shor B, Zhang WG, Toral-Barza L, Lucas J, Abraham RT, Gibbons JJ, Yu K. A new pharmacologic action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis. Cancer Res 2008; 68:2934 - 43; http://dx.doi.org/10.1158/0008-5472.CAN-07-6487; PMID: 18413763
  • Huang MT. Harringtonine, an inhibitor of initiation of protein biosynthesis. Mol Pharmacol 1975; 11:511 - 9; PMID: 1237080
  • Fresno M, Jiménez A, Vázquez D. Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem 1977; 72:323 - 30; http://dx.doi.org/10.1111/j.1432-1033.1977.tb11256.x; PMID: 319998
  • Gürel G, Blaha G, Moore PB, Steitz TA. U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome. J Mol Biol 2009; 389:146 - 56; http://dx.doi.org/10.1016/j.jmb.2009.04.005; PMID: 19362093
  • Wetzler M, Segal D. Omacetaxine as an anticancer therapeutic: what is old is new again. Curr Pharm Des 2011; 17:59 - 64; http://dx.doi.org/10.2174/138161211795049778; PMID: 21294709
  • Memmott RM, Dennis PA. Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal 2009; 21:656 - 64; http://dx.doi.org/10.1016/j.cellsig.2009.01.004; PMID: 19166931
  • Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB, Meric-Bernstam F. Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res 2004; 10:7031 - 42; http://dx.doi.org/10.1158/1078-0432.CCR-04-0361; PMID: 15501983
  • Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, et al, Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356:2271 - 81; http://dx.doi.org/10.1056/NEJMoa066838; PMID: 17538086
  • Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, et al, RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372:449 - 56; http://dx.doi.org/10.1016/S0140-6736(08)61039-9; PMID: 18653228
  • Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, et al, RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011; 364:514 - 23; http://dx.doi.org/10.1056/NEJMoa1009290; PMID: 21306238
  • Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2013; 381:125 - 32; http://dx.doi.org/10.1016/S0140-6736(12)61134-9; PMID: 23158522
  • Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2013; 381:817 - 24; http://dx.doi.org/10.1016/S0140-6736(12)61767-X; PMID: 23312829
  • Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, Pritchard K, Eisen A, Vandenberg T, Taylor M, et al. Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol 2009; 27:4536 - 41; http://dx.doi.org/10.1200/JCO.2008.21.3033; PMID: 19687332
  • Boulay A, Rudloff J, Ye J, Zumstein-Mecker S, O’Reilly T, Evans DB, Chen S, Lane HA. Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res 2005; 11:5319 - 28; http://dx.doi.org/10.1158/1078-0432.CCR-04-2402; PMID: 16033851
  • Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol 2012; 30:2718 - 24; http://dx.doi.org/10.1200/JCO.2011.39.0708; PMID: 22565002
  • Baselga J, Semiglazov V, van Dam P, Manikhas A, Bellet M, Mayordomo J, Campone M, Kubista E, Greil R, Bianchi G, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009; 27:2630 - 7; http://dx.doi.org/10.1200/JCO.2008.18.8391; PMID: 19380449
  • Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366:520 - 9; http://dx.doi.org/10.1056/NEJMoa1109653; PMID: 22149876
  • Beaver JA, Park BH. The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptor-positive advanced breast cancer. Future Oncol 2012; 8:651 - 7; http://dx.doi.org/10.2217/fon.12.49; PMID: 22764762
  • Wolff AC, Lazar AA, Bondarenko I, Garin AM, Brincat S, Chow L, Sun Y, Neskovic-Konstantinovic Z, Guimaraes RC, Fumoleau P, et al. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol 2013; 31:195 - 202; http://dx.doi.org/10.1200/JCO.2011.38.3331; PMID: 23233719
  • Mazzoletti M, Bortolin F, Brunelli L, Pastorelli R, Di Giandomenico S, Erba E, Ubezio P, Broggini M. Combination of PI3K/mTOR inhibitors: antitumor activity and molecular correlates. Cancer Res 2011; 71:4573 - 84; http://dx.doi.org/10.1158/0008-5472.CAN-10-4322; PMID: 21602434
  • Li T, Wang J, Wang X, Yang N, Chen SM, Tong LJ, Yang CH, Meng LH, Ding J. WJD008, a dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin inhibitor, prevents PI3K signaling and inhibits the proliferation of transformed cells with oncogenic PI3K mutant. J Pharmacol Exp Ther 2010; 334:830 - 8; http://dx.doi.org/10.1124/jpet.110.167940; PMID: 20522531
  • Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, Botero ML, Llonch E, Atzori F, Di Cosimo S, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008; 68:8022 - 30; http://dx.doi.org/10.1158/0008-5472.CAN-08-1385; PMID: 18829560
  • Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4:648 - 57; http://dx.doi.org/10.1038/ncb839; PMID: 12172553
  • National Cancer Institute. Phase II Trial of Akt Inhibitor MK2206 in Patients With Advanced Breast Cancer Who Have Tumors With a PIK3CA Mutation, or an AKT Mutation, and/or PTEN Loss/PTEN Mutation. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2011- [cited 2014 March 27]. Available from: http://clinicaltrials.gov/ct2/show/NCT01277757 NLM identifier: NCT01277757.
  • QuantumLeap Healthcare Collaborative. I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2009- [cited 2014 March 27]. Available from: http://clinicaltrials.gov/ct2/show/NCT01042379 NLM identifier: NCT01042379.
  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177 - 82; http://dx.doi.org/10.1126/science.3798106; PMID: 3798106
  • Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 2008; 118:3065 - 74; PMID: 18725988
  • Carrière A, Cargnello M, Julien LA, Gao H, Bonneil E, Thibault P, Roux PP. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biol 2008; 18:1269 - 77; http://dx.doi.org/10.1016/j.cub.2008.07.078; PMID: 18722121
  • Carriere A, Romeo Y, Acosta-Jaquez HA, Moreau J, Bonneil E, Thibault P, Fingar DC, Roux PP. ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). J Biol Chem 2011; 286:567 - 77; http://dx.doi.org/10.1074/jbc.M110.159046; PMID: 21071439
  • Wheater MJ, Johnson PW, Blaydes JP. The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival. Cancer Biol Ther 2010; 10:728 - 35; http://dx.doi.org/10.4161/cbt.10.7.12965; PMID: 20686366
  • Konicek BW, Stephens JR, McNulty AM, Robichaud N, Peery RB, Dumstorf CA, Dowless MS, Iversen PW, Parsons S, Ellis KE, et al. Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases. Cancer Res 2011; 71:1849 - 57; http://dx.doi.org/10.1158/0008-5472.CAN-10-3298; PMID: 21233335
  • Hvidtfeldt UA, Gunter MJ, Lange T, Chlebowski RT, Lane D, Farhat GN, Freiberg MS, Keiding N, Lee JS, Prentice R, et al. Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption, and breast cancer. Cancer Epidemiol Biomarkers Prev 2012; 21:1203 - 12; http://dx.doi.org/10.1158/1055-9965.EPI-12-0310; PMID: 22564867
  • Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 2009; 27:3297 - 302; http://dx.doi.org/10.1200/JCO.2009.19.6410; PMID: 19487376
  • Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE, Thor AD. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 2009; 8:909 - 15; http://dx.doi.org/10.4161/cc.8.6.7933; PMID: 19221498
  • Liu H, Scholz C, Zang C, Schefe JH, Habbel P, Regierer AC, Schulz CO, Possinger K, Eucker J. Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro. Anticancer Res 2012; 32:1627 - 37; PMID: 22593441
  • Col NF, Ochs L, Springmann V, Aragaki AK, Chlebowski RT. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat 2012; 135:639 - 46; http://dx.doi.org/10.1007/s10549-012-2170-x; PMID: 22847511
  • Niraula S, Dowling RJ, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready DR, Reedijk M, et al. Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat 2012; 135:821 - 30; http://dx.doi.org/10.1007/s10549-012-2223-1; PMID: 22933030
  • Chen Y, Li S. Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia. Onco Targets Ther 2014; 7:177 - 86; PMID: 24516334
  • Cortes JE, Nicolini FE, Wetzler M, Lipton JH, Akard L, Craig A, Nanda N, Benichou AC, Leonoudakis J, Khoury HJ, et al. Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib. Clin Lymphoma Myeloma Leuk 2013; 13:584 - 91; http://dx.doi.org/10.1016/j.clml.2013.03.020; PMID: 23787123