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2000
Volume 32, Issue 17
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Cancer immunotherapy has demonstrated remarkable success in the treatment of multiple advanced malignancies, especially approaches to target the immune checkpoint. Nonetheless, the limited response rate remains a barrier to broader application. Identifying other ways to extend the beneficiaries to a large extent is needed. Emerging evidence has shown that mitogen-activated protein kinase-interacting kinases (MNKs) could be regarded as a novel, attractive target for cancer immunotherapy that is closely correlated with cancer biology and therapies. A comprehensive understanding of the role and mechanism of MNKs in cancer will shed light on the discovery of novel therapeutic strategies for cancer treatment. In this review, we outlined the structure of MNKs, their function and expression, and how MNKs affect tumor progression and elucidated the evidence supporting MNKs as a new promising treatment modality in human cancers.

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2025-10-11

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References

  1. Ramos-CasalsM. BrahmerJ.R. CallahanM.K. Flores-ChávezA. KeeganN. KhamashtaM.A. LambotteO. MarietteX. PratA. Suárez-AlmazorM.E. Immune-related adverse events of checkpoint inhibitors.Nat. Rev. Dis. Primers2020613810.1038/s41572‑020‑0160‑632382051
     [Google Scholar]
  2. LiuM. GuoF. Recent updates on cancer immunotherapy.Precis. Clin. Med.201812657410.1093/pcmedi/pby01130687562
     [Google Scholar]
  3. EgenJ.G. OuyangW. WuL.C. Human anti-tumor immunity: Insights from immunotherapy clinical trials.Immunity2020521365410.1016/j.immuni.2019.12.01031940272
     [Google Scholar]
  4. KraehenbuehlL. WengC.H. EghbaliS. WolchokJ.D. MerghoubT. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways.Nat. Rev. Clin. Oncol.2022191375010.1038/s41571‑021‑00552‑734580473
     [Google Scholar]
  5. HauthF. HoA.Y. FerroneS. DudaD.G. Radiotherapy to enhance chimeric antigen receptor t-cell therapeutic efficacy in solid tumors.JAMA Oncol.2021771051105910.1001/jamaoncol.2021.016833885725
     [Google Scholar]
  6. LiH. Er SawP. SongE. Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics.Cell. Mol. Immunol.202017545146110.1038/s41423‑020‑0417‑832313210
     [Google Scholar]
  7. SaxenaM. van der BurgS.H. MeliefC.J.M. BhardwajN. Therapeutic cancer vaccines.Nat. Rev. Cancer202121636037810.1038/s41568‑021‑00346‑033907315
     [Google Scholar]
  8. KaufmanH.L. KohlhappF.J. ZlozaA. Oncolytic viruses: A new class of immunotherapy drugs.Nat. Rev. Drug Discov.201514964266210.1038/nrd466326323545
     [Google Scholar]
  9. HanX. LiH. ZhouD. ChenZ. GuZ. Local and targeted delivery of immune checkpoint blockade therapeutics.Acc. Chem. Res.202053112521253310.1021/acs.accounts.0c0033933073988
     [Google Scholar]
  10. HavelJ.J. ChowellD. ChanT.A. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy.Nat. Rev. Cancer201919313315010.1038/s41568‑019‑0116‑x30755690
     [Google Scholar]
  11. O’DonnellJ.S. TengM.W.L. SmythM.J. Cancer immunoediting and resistance to T cell-based immunotherapy.Nat. Rev. Clin. Oncol.201916315116710.1038/s41571‑018‑0142‑830523282
     [Google Scholar]
  12. RezatabarS. KarimianA. RameshkniaV. ParsianH. MajidiniaM. KopiT.A. BishayeeA. SadeghiniaA. YousefiM. MonirialamdariM. YousefiB. RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression.J. Cell. Physiol.20192349149511496510.1002/jcp.2833430811039
     [Google Scholar]
  13. AnjumJ. MitraS. DasR. AlamR. MojumderA. EmranT.B. IslamF. RaufA. HossainM.J. AljohaniA.S.M. AbdulmonemW.A. AlsharifK.F. AlzahraniK.J. KhanH. A renewed concept on the MAPK signaling pathway in cancers: Polyphenols as a choice of therapeutics.Pharmacol. Res.202218410639810.1016/j.phrs.2022.10639835988867
     [Google Scholar]
  14. WaskiewiczA.J. FlynnA. ProudC.G. CooperJ.A. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2.EMBO J.19971681909192010.1093/emboj/16.8.19099155017
     [Google Scholar]
  15. FukunagaR. HunterT. MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates.EMBO J.19971681921193310.1093/emboj/16.8.19219155018
     [Google Scholar]
  16. Pinto-DíezC. Ferreras-MartínR. Carrión-MarchanteR. GonzálezV.M. MartínM.E. Deeping in the role of the map-kinases interacting kinases (MNKs) in cancer.Int. J. Mol. Sci.2020218296710.3390/ijms2108296732340135
     [Google Scholar]
  17. HouS. DuP. WangP. WangC. LiuP. LiuH. Significance of MNK1 in prognostic prediction and chemotherapy development of epithelial ovarian cancer.Clin. Transl. Oncol.20171991107111610.1007/s12094‑017‑1646‑x28332091
     [Google Scholar]
  18. ZhengJ. LiJ. XuL. XieG. WenQ. LuoJ. LiD. HuangD. FanS. Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma.PLoS One201492e8922010.1371/journal.pone.008922024551240
     [Google Scholar]
  19. YangX. LiuZ. YinX. ZengY. GuoG. Inhibition MNK-eIF4E-β-catenin preferentially sensitizes gastric cancer to chemotherapy.Fundam. Clin. Pharmacol.202236471272010.1111/fcp.1275935048413
     [Google Scholar]
  20. ZhangQ. LiH. LiQ. MNK/eIF4E inhibition overcomes anlotinib resistance in non-small cell lung cancer.Fundam. Clin. Pharmacol.20223722455236355605
     [Google Scholar]
  21. ZhuY. WangC. LiM. YangX. Targeting of MNK/eIF4E overcomes chemoresistance in cervical cancer.J. Pharm. Pharmacol.202173101418142610.1093/jpp/rgab09434254647
     [Google Scholar]
  22. XuY. LiaoS. WangL. WangY. WeiW. SuK. TuY. ZhuS. Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin.Cancer Chemother. Pharmacol.2021871859310.1007/s00280‑020‑04195‑w33159561
     [Google Scholar]
  23. PhamT.N.D. SpauldingC. MunshiH.G. Controlling time: How MNK kinases function to shape tumor immunity.Cancers2020128209610.3390/cancers1208209632731503
     [Google Scholar]
  24. UedaT. Watanabe-FukunagaR. FukuyamaH. NagataS. FukunagaR. Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or development.Mol. Cell. Biol.200424156539654910.1128/MCB.24.15.6539‑6549.200415254222
     [Google Scholar]
  25. HouJ. LamF. ProudC. WangS. Targeting Mnks for cancer therapy.Oncotarget20123211813110.18632/oncotarget.45322392765
     [Google Scholar]
  26. O’LoghlenA. GonzálezV.M. JuradoT. SalinasM. MartínM.E. Characterization of the activity of human MAP kinase-interacting kinase Mnk1b.Biochim. Biophys. Acta Mol. Cell Res.2007177391416142710.1016/j.bbamcr.2007.05.00917590453
     [Google Scholar]
  27. O’LoghlenA. GonzálezV.M. PiñeiroD. Pérez-MorgadoM.I. SalinasM. MartínM.E. Identification and molecular characterization of Mnk1b, a splice variant of human MAP kinase-interacting kinase Mnk1.Exp. Cell Res.2004299234335510.1016/j.yexcr.2004.06.00615350534
     [Google Scholar]
  28. ScheperG.C. ParraJ.L. WilsonM. van KollenburgB. VertegaalA.C.O. HanZ.G. ProudC.G. The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization.Mol. Cell. Biol.200323165692570510.1128/MCB.23.16.5692‑5705.200312897141
     [Google Scholar]
  29. BramhamC.R. JensenK.B. ProudC.G. Tuning specific translation in cancer metastasis and synaptic memory: Control at the MNK–eIF4E axis.Trends Biochem. Sci.2016411084785810.1016/j.tibs.2016.07.00827527252
     [Google Scholar]
  30. ParraJ.L. BuxadéM. ProudC.G. Features of the catalytic domains and C termini of the MAPK signal-integrating kinases Mnk1 and Mnk2 determine their differing activities and regulatory properties.J. Biol. Chem.200528045376233763310.1074/jbc.M50835620016162500
     [Google Scholar]
  31. GotoS. YaoZ. ProudC.G. The C-terminal domain of Mnk1a plays a dual role in tightly regulating its activity.Biochem. J.2009423227929010.1042/BJ2009022819650764
     [Google Scholar]
  32. BuxadeM. Parra-PalauJ.L. ProudC.G. The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases).Front. Biosci.2008Volume135359537310.2741/308618508592
     [Google Scholar]
  33. BuxadéM. MorriceN. KrebsD.L. ProudC.G. The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha.J. Biol. Chem.20082831576510.1074/jbc.M70528620017965020
     [Google Scholar]
  34. BuxadéM. ParraJ.L. RousseauS. ShpiroN. MarquezR. MorriceN. BainJ. EspelE. ProudC.G. The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNP A1.Immunity200523217718910.1016/j.immuni.2005.06.00916111636
     [Google Scholar]
  35. GingrasA.C. RaughtB. SonenbergN. eIF4 initiation factors: Effectors of mRNA recruitment to ribosomes and regulators of translation.Annu. Rev. Biochem.199968191396310.1146/annurev.biochem.68.1.91310872469
     [Google Scholar]
  36. MoyJ.K. KhoutorskyA. AsieduM.N. BlackB.J. KuhnJ.L. Barragán-IglesiasP. MegatS. BurtonM.D. Burgos-VegaC.C. MelemedjianO.K. BoitanoS. VagnerJ. GkogkasC.G. PancrazioJ.J. MogilJ.S. DussorG. SonenbergN. PriceT.J. The MNK–eIF4E signaling axis contributes to injury-induced nociceptive plasticity and the development of chronic pain.J. Neurosci.201737317481749910.1523/JNEUROSCI.0220‑17.201728674170
     [Google Scholar]
  37. RowlettR.M. ChrestensenC.A. NyceM. HarpM.G. PeloJ.W. CominelliF. ErnstP.B. PizarroT.T. SturgillT.W. WorthingtonM.T. MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages.Am. J. Physiol. Gastrointest. Liver Physiol.20082942G452G45910.1152/ajpgi.00077.200718032482
     [Google Scholar]
  38. JoshiS. PlataniasL.C. Mnk kinases in cytokine signaling and regulation of cytokine responses.Biomol. Concepts20123212713910.1515/bmc‑2011‑105723710261
     [Google Scholar]
  39. SandemanL.Y. KangW.X. WangX. JensenK.B. WongD. BoT. GaoL. ZhaoJ. ByrneC.D. PageA.J. ProudC.G. Disabling MNK protein kinases promotes oxidative metabolism and protects against diet-induced obesity.Mol. Metab.20204210105410.1016/j.molmet.2020.10105432712434
     [Google Scholar]
  40. AmorimI.S. KediaS. KoulouliaS. SimbrigerK. GantoisI. JafarnejadS.M. LiY. KampaiteA. PootersT. RomanòN. GkogkasC.G. Loss of eIF4E phosphorylation engenders depression-like behaviors via selective mRNA translation.J. Neurosci.20183882118213310.1523/JNEUROSCI.2673‑17.201829367404
     [Google Scholar]
  41. ShimadaN. RiosI. MoranH. SayersB. HubbardK. p38 MAP kinase-dependent regulation of the expression level and subcellular distribution of heterogeneous nuclear ribonucleoprotein a1 and its involvement in cellular senescence in normal human fibroblasts.RNA Biol.20096329330410.4161/rna.6.3.849719430204
     [Google Scholar]
  42. JoshiS. PlataniasL.C. Mnk kinase pathway: Cellular functions and biological outcomes.World J. Biol. Chem.20145332133310.4331/wjbc.v5.i3.32125225600
     [Google Scholar]
  43. FortinC.F. MayerT.Z. CloutierA. McDonaldP.P. Translational control of human neutrophil responses by MNK1.J. Leukoc. Biol.201394469370310.1189/jlb.011301223401599
     [Google Scholar]
  44. Shav-TalY. ZiporiD. PSF and p54 nrb /NonO – multi-functional nuclear proteins.FEBS Lett.2002531210911410.1016/S0014‑5793(02)03447‑612417296
     [Google Scholar]
  45. HefnerY. Börsch-HauboldA.G. MurakamiM. WildeJ.I. PasquetS. SchieltzD. GhomashchiF. YatesJ.R.III ArmstrongC.G. PatersonA. CohenP. FukunagaR. HunterT. KudoI. WatsonS.P. GelbM.H. Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.J. Biol. Chem.200027548375423755110.1074/jbc.M00339520010978317
     [Google Scholar]
  46. KarakiS. AndrieuC. ZiouziouH. RocchiP. The eukaryotic translation initiation factor 4E (eIF4E) as a therapeutic target for cancer.Adv. Protein Chem. Struct. Biol.201510112610.1016/bs.apcsb.2015.09.00126572974
     [Google Scholar]
  47. LinehamE. TizzardG.J. ColesS.J. SpencerJ. MorleyS.J. Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/ mTOR pathways on cell migration in MDA-MB-231 cells.Oncotarget2018918141481415910.18632/oncotarget.2435429581834
     [Google Scholar]
  48. Lazaris-KaratzasA. MontineK.S. SonenbergN. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap.Nature1990345627554454710.1038/345544a02348862
     [Google Scholar]
  49. De BenedettiA. HarrisA.L. eIF4E expression in tumors: Its possible role in progression of malignancies.Int. J. Biochem. Cell Biol.1999311597210.1016/S1357‑2725(98)00132‑010216944
     [Google Scholar]
  50. DiabS. KumarasiriM. YuM. TeoT. ProudC. MilneR. WangS. MAP kinase-interacting kinases--emerging targets against cancer.Chem. Biol.201421444145210.1016/j.chembiol.2014.01.01124613018
     [Google Scholar]
  51. WenQ. WangW. LuoJ. ChuS. ChenL. XuL. ZangH. AlnemahM.M. MaJ. FanS. CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating mitochondrial apoptotic pathway.Oncotarget2016719277872780110.18632/oncotarget.849727050281
     [Google Scholar]
  52. HanahanD. WeinbergR.A. The hallmarks of cancer.Cell20001001577010.1016/S0092‑8674(00)81683‑910647931
     [Google Scholar]
  53. HanahanD. WeinbergR.A. Hallmarks of cancer: The next generation.Cell2011144564667410.1016/j.cell.2011.02.01321376230
     [Google Scholar]
  54. KolchW. HalaszM. GranovskayaM. KholodenkoB.N. The dynamic control of signal transduction networks in cancer cells.Nat. Rev. Cancer201515951552710.1038/nrc398326289315
     [Google Scholar]
  55. ZhaoM. MishraL. DengC.X. The role of TGF-β/SMAD4 signaling in cancer.Int. J. Biol. Sci.201814211112310.7150/ijbs.2323029483830
     [Google Scholar]
  56. MassaguéJ. TGFβ in Cancer.Cell2008134221523010.1016/j.cell.2008.07.00118662538
     [Google Scholar]
  57. ColakS. ten DijkeP. Targeting TGF-β signaling in cancer.Trends Cancer201731567110.1016/j.trecan.2016.11.00828718426
     [Google Scholar]
  58. GrzmilM. MorinP.Jr LinoM.M. MerloA. FrankS. WangY. MoncayoG. HemmingsB.A. MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-β signaling pathway in human glioblastoma.Cancer Res.20117162392240210.1158/0008‑5472.CAN‑10‑311221406405
     [Google Scholar]
  59. MoustakasA. HeldinC.H. The regulation of TGFβ signal transduction.Development2009136223699371410.1242/dev.03033819855013
     [Google Scholar]
  60. JitariuA.A. RaicaM. CîmpeanA.M. SuciuS.C. The role of PDGF-B/PDGFR-BETA axis in the normal development and carcinogenesis of the breast.Crit. Rev. Oncol. Hematol.2018131465210.1016/j.critrevonc.2018.08.00230293705
     [Google Scholar]
  61. WheaterM.J. JohnsonP.W.M. BlaydesJ.P. The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival.Cancer Biol. Ther.201010772873510.4161/cbt.10.7.1296520686366
     [Google Scholar]
  62. KleinerH.E. KrishnanP. TubbsJ. SmithM. MeschonatC. ShiR. Lowery-NordbergM. AdegboyegaP. UngerM. CardelliJ. ChuQ. MathisJ.M. CliffordJ. De BenedettiA. LiB.D.L. Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer.J. Exp. Clin. Cancer Res.2009281510.1186/1756‑9966‑28‑519134194
     [Google Scholar]
  63. YeungK.T. YangJ. Epithelial–mesenchymal transition in tumor metastasis.Mol. Oncol.2017111283910.1002/1878‑0261.1201728085222
     [Google Scholar]
  64. LambertA.W. PattabiramanD.R. WeinbergR.A. Emerging biological principles of metastasis.Cell2017168467069110.1016/j.cell.2016.11.03728187288
     [Google Scholar]
  65. DiepenbruckM. ChristoforiG. Epithelial–mesenchymal transition (EMT) and metastasis: Yes, no, maybe?Curr. Opin. Cell Biol.20164371310.1016/j.ceb.2016.06.00227371787
     [Google Scholar]
  66. RamalingamS. RamamurthyV. GediyaL. MurigiF. PurushottamacharP. HuangW. ChoiE. ZhangY. VasaitisT. KaneM. LapidusR. NjarV. The novel Mnk1/2 degrader and apoptosis inducer VNLG-152 potently inhibits TNBC tumor growth and metastasis.Cancers201911329910.3390/cancers1103029930832411
     [Google Scholar]
  67. RamamurthyV.P. RamalingamS. GediyaL.K. NjarV.C.O. The retinamide VNLG -152 inhibits f-AR / AR -V7 and MNK – eIF 4E signaling pathways to suppress EMT and castration-resistant prostate cancer xenograft growth.FEBS J.201828561051106310.1111/febs.1438329323792
     [Google Scholar]
  68. RamamurthyV.P. RamalingamS. GediyaL. Kwegyir-AffulA.K. NjarV.C.O. Simultaneous targeting of androgen receptor (AR) and MAPK-interacting kinases (MNKs) by novel retinamides inhibits growth of human prostate cancer cell lines.Oncotarget2015653195321010.18632/oncotarget.308425605250
     [Google Scholar]
  69. ChenS. CuiL. HuQ. ShenY. JiangY. ZhaoJ. Preclinical evidence that MNK/eIF4E inhibition by cercosporamide enhances the response to antiangiogenic TKI and mTOR inhibitor in renal cell carcinoma.Biochem. Biophys. Res. Commun.2020530114214810.1016/j.bbrc.2020.06.13332828276
     [Google Scholar]
  70. BuchananC. Lago HuvelleM.A. PetersM.G. Metastasis suppressors: Basic and translational advances.Curr. Pharm. Biotechnol.201112111948196010.2174/13892011179837691421470135
     [Google Scholar]
  71. KonicekB.W. StephensJ.R. McNultyA.M. RobichaudN. PeeryR.B. DumstorfC.A. DowlessM.S. IversenP.W. ParsonsS. EllisK.E. McCannD.J. PelletierJ. FuricL. YinglingJ.M. StancatoL.F. SonenbergN. GraffJ.R. Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases.Cancer Res.20117151849185710.1158/0008‑5472.CAN‑10‑329821233335
     [Google Scholar]
  72. TianS. WangX. ProudC.G. Oncogenic MNK signalling regulates the metastasis suppressor NDRG1.Oncotarget2017828461214613510.18632/oncotarget.1755528545025
     [Google Scholar]
  73. MoranaO. WoodW. GregoryC.D. The apoptosis paradox in cancer.Int. J. Mol. Sci.2022233132810.3390/ijms2303132835163253
     [Google Scholar]
  74. WongR. Apoptosis in cancer: From pathogenesis to treatment[J].Journal of experimental & clinical cancer research.CR (East Lansing Mich.)201130187
     [Google Scholar]
  75. PolunovskyV.A. GingrasA.C. SonenbergN. PetersonM. TanA. RubinsJ.B. ManivelJ.C. BittermanP.B. Translational control of the antiapoptotic function of Ras.J. Biol. Chem.200027532247762478010.1074/jbc.M00193820010811643
     [Google Scholar]
  76. AdamsK.W. CooperG.M. Rapid turnover of mcl-1 couples translation to cell survival and apoptosis.J. Biol. Chem.200728296192620010.1074/jbc.M61064320017200126
     [Google Scholar]
  77. WendelH.G. SilvaR.L.A. MalinaA. MillsJ.R. ZhuH. UedaT. Watanabe-FukunagaR. FukunagaR. Teruya-FeldsteinJ. PelletierJ. LoweS.W. Dissecting eIF4E action in tumorigenesis.Genes Dev.20072124000.200010.1101/gad.160440718055695
     [Google Scholar]
  78. AdessoL. CalabrettaS. BarbagalloF. CapursoG. PilozziE. GeremiaR. Delle FaveG. SetteC. Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway.Oncogene201332232848285710.1038/onc.2012.30622797067
     [Google Scholar]
  79. GrzmilM. SeebacherJ. HessD. BeheM. SchibliR. MoncayoG. FrankS. HemmingsB.A. Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.Cell. Signal.20162891412142110.1016/j.cellsig.2016.06.00527289018
     [Google Scholar]
  80. AstaneheA. FinkbeinerM.R. KrzywinskiM. FotovatiA. DhillonJ. BerquinI.M. MillsG.B. MarraM.A. DunnS.E. MKNK1 is a YB-1 target gene responsible for imparting trastuzumab resistance and can be blocked by RSK inhibition.Oncogene201231414434444610.1038/onc.2011.61722249268
     [Google Scholar]
  81. GeterP.A. ErnlundA.W. BakogianniS. AlardA. ArjuR. GiashuddinS. GadiA. BrombergJ. SchneiderR.J. Hyperactive mTOR and MNK1 phosphorylation of eIF4E confer tamoxifen resistance and estrogen independence through selective mRNA translation reprogramming.Genes Dev.201731222235224910.1101/gad.305631.11729269484
     [Google Scholar]
  82. VimalrajS. A concise review of VEGF, PDGF, FGF, Notch, angiopoietin, and HGF signalling in tumor angiogenesis with a focus on alternative approaches and future directions.Int. J. Biol. Macromol.20222211428143810.1016/j.ijbiomac.2022.09.12936122781
     [Google Scholar]
  83. FukumuraD. KloepperJ. AmoozgarZ. DudaD.G. JainR.K. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges.Nat. Rev. Clin. Oncol.201815532534010.1038/nrclinonc.2018.2929508855
     [Google Scholar]
  84. MariottiV FiorottoR CadamuroM New insights on the role of vascular endothelial growth factor in biliary pathophysiologyJHEP Rep202133100251
     [Google Scholar]
  85. RamjiawanR.R. GriffioenA.W. DudaD.G. Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?Angiogenesis201720218520410.1007/s10456‑017‑9552‑y28361267
     [Google Scholar]
  86. MuzB. de la PuenteP. AzabF. AzabA.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy.Hypoxia20153839210.2147/HP.S9341327774485
     [Google Scholar]
  87. ChungJ. BachelderR.E. LipscombE.A. ShawL.M. MercurioA.M. Integrin (α6β4) regulation of eIF-4E activity and VEGF translation.J. Cell Biol.2002158116517410.1083/jcb.20011201512105188
     [Google Scholar]
  88. KorneevaN.L. SoungY.H. KimH.I. GiordanoA. RhoadsR.E. GramH. ChungJ. Mnk mediates integrin α6β4-dependent eIF4E phosphorylation and translation of VEGF mRNA.Mol. Cancer Res.20108121571157810.1158/1541‑7786.MCR‑10‑009121047768
     [Google Scholar]
  89. LiuY. SunL. SuX. GuoS. Inhibition of eukaryotic initiation factor 4E phosphorylation by cercosporamide selectively suppresses angiogenesis, growth and survival of human hepatocellular carcinoma.Biomed. Pharmacother.20168423724310.1016/j.biopha.2016.09.03827662474
     [Google Scholar]
  90. YangS. HewittS. SteinbergS. LiewehrD. SwainS. Expression levels of eIF4E, VEGF, and cyclin D1, and correlation of eIF4E with VEGF and cyclin D1 in multi-tumor tissue microarray.Oncol. Rep.200717228128710.3892/or.17.2.28117203162
     [Google Scholar]
  91. BrombergJ. WangT.C. Inflammation and cancer: IL-6 and STAT3 complete the link.Cancer Cell2009152798010.1016/j.ccr.2009.01.00919185839
     [Google Scholar]
  92. CarswellE.A. OldL.J. KasselR.L. GreenS. FioreN. WilliamsonB. An endotoxin-induced serum factor that causes necrosis of tumors.Proc. Natl. Acad. Sci. USA19757293666367010.1073/pnas.72.9.36661103152
     [Google Scholar]
  93. SchallT.J. BaconK. ToyK.J. GoeddelD.V. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES.Nature1990347629466967110.1038/347669a01699135
     [Google Scholar]
  94. LoetscherP. SeitzM. Clark-LewisI. BaggioliniM. MoserB. Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release.J. Immunol.1996156132232710.4049/jimmunol.156.1.3228598480
     [Google Scholar]
  95. DieuM.C. VanbervlietB. VicariA. BridonJ.M. OldhamE. Aït-YahiaS. BrièreF. ZlotnikA. LebecqueS. CauxC. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.J. Exp. Med.1998188237338610.1084/jem.188.2.3739670049
     [Google Scholar]
  96. NikolchevaT. PyronnetS. ChouS. SonenbergN. SongA. ClaybergerC. KrenskyA.M. A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes.J. Clin. Invest.2002110111912610.1172/JCI021533612093895
     [Google Scholar]
  97. FridmanW.H. TartourE. Macrophage- and lymphocyte-produced Th1 and Th2 cytokines in the tumour microenvironment.Res. Immunol.19981497-865165310.1016/S0923‑2494(99)80033‑99851518
     [Google Scholar]
  98. HoshinoH. LötvallJ. SkooghB.E. LindénA. Neutrophil recruitment by interleukin-17 into rat airways in vivo. Role of tachykinins.Am. J. Respir. Crit. Care Med.199915951423142810.1164/ajrccm.159.5.980600810228105
     [Google Scholar]
  99. NoubadeR. KrementsovD.N. del RioR. ThorntonT. NagaleekarV. SaligramaN. SpitzackA. SpachK. SabioG. DavisR.J. RinconM. TeuscherC. Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis.Blood2011118123290330010.1182/blood‑2011‑02‑33655221791428
     [Google Scholar]
  100. CherlaR.P. LeeS.Y. MeesP.L. TeshV.L. Shiga toxin 1-induced cytokine production is mediated by MAP kinase pathways and translation initiation factor eIF4E in the macrophage-like THP-1 cell line.J. Leukoc. Biol.200579239740710.1189/jlb.060531316301326
     [Google Scholar]
  101. PlataniasL.C. Mechanisms of type-I- and type-II-interferon-mediated signalling.Nat. Rev. Immunol.20055537538610.1038/nri160415864272
     [Google Scholar]
  102. BordenE.C. SenG.C. UzeG. SilvermanR.H. RansohoffR.M. FosterG.R. StarkG.R. Interferons at age 50: past, current and future impact on biomedicine.Nat. Rev. Drug Discov.200761297599010.1038/nrd242218049472
     [Google Scholar]
  103. JoshiS. KaurS. RedigA.J. GoldsboroughK. DavidK. UedaT. Watanabe-FukunagaR. BakerD.P. FishE.N. FukunagaR. PlataniasL.C. Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses.Proc. Natl. Acad. Sci. USA200910629120971210210.1073/pnas.090056210619574459
     [Google Scholar]
  104. MorganD.A. RuscettiF.W. GalloR. Selective in vitro growth of T lymphocytes from normal human bone marrows.Science197619342571007100810.1126/science.181845181845
     [Google Scholar]
  105. BamfordR.N. GrantA.J. BurtonJ.D. PetersC. KurysG. GoldmanC.K. BrennanJ. RoesslerE. WaldmannT.A. The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells.Proc. Natl. Acad. Sci. USA199491114940494410.1073/pnas.91.11.49408197161
     [Google Scholar]
  106. GrabsteinK.H. EisenmanJ. ShanebeckK. RauchC. SrinivasanS. FungV. BeersC. RichardsonJ. SchoenbornM.A. AhdiehM. JohnsonL. AldersonM.R. WatsonJ.D. AndersonD.M. GiriJ.G. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor.Science1994264516196596810.1126/science.81781558178155
     [Google Scholar]
  107. GrundE.M. SpyropoulosD.D. WatsonD.K. Muise-HelmericksR.C. Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells.J. Biol. Chem.200528064772477810.1074/jbc.M40835620015563472
     [Google Scholar]
  108. WahlS.M. Transforming growth factor beta (TGF-?) in inflammation: A cause and a cure.J. Clin. Immunol.1992122617410.1007/BF009181351313827
     [Google Scholar]
  109. ZhangY.L. DongC. MAP kinases in immune responses.Cell. Mol. Immunol.200521202716212907
     [Google Scholar]
  110. CondeelisJ. PollardJ.W. Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis.Cell2006124226326610.1016/j.cell.2006.01.00716439202
     [Google Scholar]
  111. QianB.Z. PollardJ.W. Macrophage diversity enhances tumor progression and metastasis.Cell20101411395110.1016/j.cell.2010.03.01420371344
     [Google Scholar]
  112. PathriaP. LouisT.L. VarnerJ.A. Targeting tumor-associated macrophages in cancer.Trends Immunol.201940431032710.1016/j.it.2019.02.00330890304
     [Google Scholar]
  113. XuH. ZhuJ. SmithS. FoldiJ. ZhaoB. ChungA.Y. OuttzH. KitajewskiJ. ShiC. WeberS. SaftigP. LiY. OzatoK. BlobelC.P. IvashkivL.B. HuX. Notch–RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization.Nat. Immunol.201213764265010.1038/ni.230422610140
     [Google Scholar]
  114. GaoC. GuoH. MiZ. WaiP.Y. KuoP.C. Transcriptional regulatory functions of heterogeneous nuclear ribonucleoprotein-U and -A/B in endotoxin-mediated macrophage expression of osteopontin.J. Immunol.2005175152353010.4049/jimmunol.175.1.52315972688
     [Google Scholar]
  115. VegliaF. PeregoM. GabrilovichD. Myeloid-derived suppressor cells coming of age.Nat. Immunol.201819210811910.1038/s41590‑017‑0022‑x29348500
     [Google Scholar]
  116. HuangF GonçalvesC GuoQ Abstract A53: Phosphorylation of eIF4E promotes phenotype switching and MDSC-mediated immunosuppression in melanomaCancer Immunol Res202083A53
     [Google Scholar]
  117. GraffJ.R. KonicekB.W. CarterJ.H. MarcussonE.G. Targeting the eukaryotic translation initiation factor 4E for cancer therapy.Cancer Res.200868363163410.1158/0008‑5472.CAN‑07‑563518245460
     [Google Scholar]
  118. RobichaudN. HsuB.E. IstomineR. AlvarezF. BlagihJ. MaE.H. MoralesS.V. DaiD.L. LiG. SouleimanovaM. GuoQ. del RinconS.V. MillerW.H.Jr Ramón y CajalS. ParkM. JonesR.G. PiccirilloC.A. SiegelP.M. SonenbergN. Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils.Proc. Natl. Acad. Sci. USA201811510E2202E220910.1073/pnas.171743911529463754
     [Google Scholar]
  119. GodfreyD.I. UldrichA.P. McCluskeyJ. RossjohnJ. MoodyD.B. The burgeoning family of unconventional T cells.Nat. Immunol.201516111114112310.1038/ni.329826482978
     [Google Scholar]
  120. BevanM.J. Helping the CD8+ T-cell response.Nat. Rev. Immunol.20044859560210.1038/nri141315286726
     [Google Scholar]
  121. RomanoM. FanelliG. AlbanyC.J. GigantiG. LombardiG. Past, present, and future of regulatory t cell therapy in transplantation and autoimmunity.Front. Immunol.2019104310.3389/fimmu.2019.0004330804926
     [Google Scholar]
  122. CrawfordA. AngelosantoJ.M. NadwodnyK.L. BlackburnS.D. WherryE.J. A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection.PLoS Pathog.201177e100209810.1371/journal.ppat.100209821814510
     [Google Scholar]
  123. PiccirilloC.A. BjurE. TopisirovicI. SonenbergN. LarssonO. Translational control of immune responses: from transcripts to translatomes.Nat. Immunol.201415650351110.1038/ni.289124840981
     [Google Scholar]
  124. BjurE. LarssonO. YurchenkoE. ZhengL. GandinV. TopisirovicI. LiS. WagnerC.R. SonenbergN. PiccirilloC.A. Distinct translational control in CD4+ T cell subsets.PLoS Genet.201395e100349410.1371/journal.pgen.100349423658533
     [Google Scholar]
  125. AkbulutS. ReddiA.L. AggarwalP. AmbardekarC. CancianiB. KimM.K.H. HixL. VilimasT. MasonJ. BassonM.A. LovattM. PowellJ. CollinsS. QuatelaS. PhillipsM. LichtJ.D. Sprouty proteins inhibit receptor-mediated activation of phosphatidylinositol-specific phospholipase C.Mol. Biol. Cell201021193487349610.1091/mbc.e10‑02‑012320719962
     [Google Scholar]
  126. ShehataH.M. KhanS. ChenE. FieldsP.E. FlavellR.A. SanjabiS. Lack of Sprouty 1 and 2 enhances survival of effector CD8 + T cells and yields more protective memory cells.Proc. Natl. Acad. Sci. USA201811538E8939E894710.1073/pnas.180832011530126987
     [Google Scholar]
  127. GigouxM. LovatoA. LeconteJ. LeungJ. SonenbergN. SuhW.K. Inducible costimulator facilitates T-dependent B cell activation by augmenting IL-4 translation.Mol. Immunol.2014591465410.1016/j.molimm.2014.01.00824486724
     [Google Scholar]
  128. QiH. T follicular helper cells in space-time.Nat. Rev. Immunol.2016161061262510.1038/nri.2016.9427573485
     [Google Scholar]
  129. TschoppC. KnaufU. BrauchleM. ZuriniM. RamageP. GlueckD. NewL. HanJ. GramH. Phosphorylation of eIF-4E on Ser 209 in response to mitogenic and inflammatory stimuli is faithfully detected by specific antibodies.Mol. Cell Biol. Res. Commun.20003420521110.1006/mcbr.2000.021710891393
     [Google Scholar]
  130. FredenhagenA. PeterH.H. New stereoselective beckmann-type rearrangement leading to ring contraction.Tetrahedron19965241235123810.1016/0040‑4020(95)00978‑7
     [Google Scholar]
  131. KaramanM.W. HerrgardS. TreiberD.K. GallantP. AtteridgeC.E. CampbellB.T. ChanK.W. CiceriP. DavisM.I. EdeenP.T. FaraoniR. FloydM. HuntJ.P. LockhartD.J. MilanovZ.V. MorrisonM.J. PallaresG. PatelH.K. PritchardS. WodickaL.M. ZarrinkarP.P. A quantitative analysis of kinase inhibitor selectivity.Nat. Biotechnol.200826112713210.1038/nbt135818183025
     [Google Scholar]
  132. BeggsJ.E. TianS. JonesG.G. XieJ. IadevaiaV. JeneiV. ThomasG. ProudC.G. The MAP kinase-interacting kinases regulate cell migration, vimentin expression and eIF4E/CYFIP1 binding.Biochem. J.20154671637610.1042/BJ2014106625588502
     [Google Scholar]
  133. BainJ. PlaterL. ElliottM. ShpiroN. HastieC.J. MclauchlanH. KlevernicI. ArthurJ.S.C. AlessiD.R. CohenP. The selectivity of protein kinase inhibitors: A further update.Biochem. J.2007408329731510.1042/BJ2007079717850214
     [Google Scholar]
  134. ZhangM. FuW. PrabhuS. MooreJ.C. KoJ. KimJ.W. DrukerB.J. TrappV. FruehaufJ. GramH. FanH.Y. OngS.T. Inhibition of polysome assembly enhances imatinib activity against chronic myelogenous leukemia and overcomes imatinib resistance.Mol. Cell. Biol.200828206496650910.1128/MCB.00477‑0818694961
     [Google Scholar]
  135. LimS. SawT.Y. ZhangM. JanesM.R. NacroK. HillJ. LimA.Q. ChangC.T. FrumanD.A. RizzieriD.A. TanS.Y. FanH. ChuahC.T.H. OngS.T. Targeting of the MNK–eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function.Proc. Natl. Acad. Sci. USA201311025E2298E230710.1073/pnas.130183811023737503
     [Google Scholar]
  136. LandonA.L. MuniandyP.A. ShettyA.C. LehrmannE. VolponL. HoungS. ZhangY. DaiB. PeroutkaR. Mazan-MamczarzK. SteinhardtJ. MahurkarA. BeckerK.G. BordenK.L. GartenhausR.B. MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL.Nat. Commun.201451541310.1038/ncomms641325403230
     [Google Scholar]
  137. DiabS. LiP. BasnetS.K.C. LuJ. YuM. AlbrechtH. MilneR.W. WangS. Unveiling new chemical scaffolds as Mnk inhibitors.Future Med. Chem.20168327128510.4155/fmc.15.19026910782
     [Google Scholar]
  138. DiabS. TeoT. KumarasiriM. LiP. YuM. LamF. BasnetS.K.C. SykesM.J. AlbrechtH. MilneR. WangS. Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as potent Mnk2 inhibitors: Synthesis, SAR analysis and biological evaluation.ChemMedChem20149596297210.1002/cmdc.20130055224677692
     [Google Scholar]
  139. TeoT. YangY. YuM. BasnetS.K.C. GillamT. HouJ. SchmidR.M. KumarasiriM. DiabS. AlbrechtH. SykesM.J. WangS. An integrated approach for discovery of highly potent and selective Mnk inhibitors: Screening, synthesis and SAR analysis.Eur. J. Med. Chem.201510353955010.1016/j.ejmech.2015.09.00826408454
     [Google Scholar]
  140. TeoT. YuM. YangY. GillamT. LamF. SykesM.J. WangS. Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells.Cancer Lett.2015357261262310.1016/j.canlet.2014.12.02925527453
     [Google Scholar]
  141. TeoT. LamF. YuM. YangY. BasnetS.K.C. AlbrechtH. SykesM.J. WangS. Pharmacologic inhibition of MNKs in acute myeloid leukemia.Mol. Pharmacol.201588238038910.1124/mol.115.09801226044548
     [Google Scholar]
  142. WuH. HuC. WangA. WeisbergE.L. ChenY. YunC-H. WangW. LiuY. LiuX. TianB. WangJ. ZhaoZ. LiangY. LiB. WangL. WangB. ChenC. BuhrlageS.J. QiZ. ZouF. NonamiA. LiY. FernandesS.M. AdamiaS. StoneR.M. GalinskyI.A. WangX. YangG. GriffinJ.D. BrownJ.R. EckM.J. LiuJ. GrayN.S. LiuQ. Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia.Leukemia201630117318110.1038/leu.2015.18026165234
     [Google Scholar]
  143. YangH. ChennamaneniL.R. HoM.W.T. AngS.H. TanE.S.W. JeyarajD.A. YeapY.S. LiuB. OngE.H. JoyJ.K. WeeJ.L.K. KwekP. RetnaP. DinieN. NguyenT.T.H. TaiS.J. ManoharanV. PendharkarV. LowC.B. ChewY.S. VuddagiriS. SangthongpitagK. ChoongM.L. LeeM.A. KannanS. VermaC.S. PoulsenA. LimS. ChuahC. OngT.S. HillJ. MatterA. NacroK. Optimization of selective mitogen-activated protein kinase interacting kinases 1 and 2 inhibitors for the treatment of blast crisis leukemia.J. Med. Chem.201861104348436910.1021/acs.jmedchem.7b0171429683667
     [Google Scholar]
  144. CherianJ. NacroK. PohZ.Y. GuoS. JeyarajD.A. WongY.X. HoM. YangH.Y. JoyJ.K. KwekZ.P. LiuB. WeeJ.L.K. OngE.H.Q. ChoongM.L. PoulsenA. LeeM.A. PendharkarV. DingL.J. ManoharanV. ChewY.S. SangthongpitagK. LimS. OngS.T. HillJ. KellerT.H. Structure–activity relationship studies of mitogen activated protein kinase interacting kinase (MNK) 1 and 2 and BCR-ABL1 inhibitors targeting chronic myeloid leukemic cells.J. Med. Chem.20165973063307810.1021/acs.jmedchem.5b0171227011159
     [Google Scholar]
  145. SantagS. SiegelF. WengnerA.M. LangeC. BömerU. EisK. PühlerF. LienauP. BergemannL. MichelsM. von NussbaumF. MumbergD. PetersenK. BAY 1143269, a novel MNK1 inhibitor, targets oncogenic protein expression and shows potent anti-tumor activity.Cancer Lett.2017390212910.1016/j.canlet.2016.12.02928043914
     [Google Scholar]
  146. XuJ. ChenA. JoyJ. XavierV.J. OngE.H.Q. HillJ. ChaiC.L.L. Rational design of resorcylic acid lactone analogues as covalent MNK1/2 kinase inhibitors by tuning the reactivity of an enamide Michael acceptor.ChemMedChem2013891483149410.1002/cmdc.20130023123929665
     [Google Scholar]
  147. ChenL.C. HuangH.L. HuangFuW.C. YenS.C. NgoS.T. WuY.W. LinT.E. SungT.Y. LienS.T. TsengH.J. PanS.L. HuangW.J. HsuK.C. Biological evaluation of selected flavonoids as inhibitors of MNKs targeting acute myeloid leukemia.J. Nat. Prod.202083102967297510.1021/acs.jnatprod.0c0051633026809
     [Google Scholar]
  148. WebsterK.R. GoelV.K. HungI.N.J. ParkerG.S. StauntonJ. NealM. MolterJ. ChiangG.G. JessenK.A. WegerskiC.J. SperryS. HuangV. ChenJ. ThompsonP.A. ApplemanJ.R. WebberS.E. SprengelerP.A. ReichS.H. eFT508, a potent and selective mitogen-activated protein kinase interacting kinase (mnk) 1 and 2 inhibitor, is efficacious in preclinical models of diffuse large B-cell lymphoma (DLBCL).Blood201512623155410.1182/blood.V126.23.1554.1554
     [Google Scholar]
  149. ReichS.H. SprengelerP.A. ChiangG.G. ApplemanJ.R. ChenJ. ClarineJ. EamB. ErnstJ.T. HanQ. GoelV.K. HanE.Z.R. HuangV. HungI.N.J. JemisonA. JessenK.A. MolterJ. MurphyD. NealM. ParkerG.S. ShaghafiM. SperryS. StauntonJ. StumpfC.R. ThompsonP.A. TranC. WebberS.E. WegerskiC.J. ZhengH. WebsterK.R. Structure-based design of pyridone–aminal EFT508 targeting dysregulated translation by selective mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) inhibition.J. Med. Chem.20186183516354010.1021/acs.jmedchem.7b0179529526098
     [Google Scholar]
  150. GopalA.K. RamchandrenR. GabrailN.Y. A phase 1-2 dose-escalation and cohort- expansion study of eft508, a selective, orally bioavailable inhibitor of mnk1 and mnk2, in patients with hematological malignancies.Blood20171304624
     [Google Scholar]
  151. FalchookG.S. InfanteJ.R. Meric-BernstamF. MillerL.L. MorisonK. VallnerD. SperryS. GoelV. ChiangG.G. WebsterK. BartonJ. PatelM.R. A phase 1 dose escalation study of eFT508, an inhibitor of mitogen-activated protein kinase-interacting serine/threonine kinase-1 (MNK-1) and MNK-2 in patients with advanced solid tumors.J. Clin. Oncol.20173515_suppl2579257910.1200/JCO.2017.35.15_suppl.2579
     [Google Scholar]
  152. HubbardJ.M. PatelM.R. Bekaii-SaabT.S. FalchookG.S. FreilichB.L. DasariA. KniselyB.T. AndersonM. ChiangG.G. WebsterK.R. SperryS. BartonJ. BendellJ.C. A phase II, open label, randomized, noncomparative study of eFT508 (tomivosertib) alone or in combination with avelumab in subjects with relapsed/refractory microsatellite stable colorectal cancer (MSS CRC).J. Clin. Oncol.20193715_supple1414510.1200/JCO.2019.37.15_suppl.e14145
     [Google Scholar]
  153. YangZ. JiangC. ZhangW. SunG. Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment.J. Transl. Med.202220127610.1186/s12967‑022‑03474‑935717238
     [Google Scholar]
  154. HuangX. YangC. HanQ. YeX. LeiW. QianW. MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: The mechanism of synergic killing of human T-ALL cells.Acta Pharmacol. Sin.201839121894190110.1038/s41401‑018‑0161‑030297804
     [Google Scholar]
  155. KnightJ.R.P. AlexandrouC. SkalkaG.L. VlahovN. PennelK. OfficerL. TeodosioA. KanellosG. GayD.M. May-WilsonS. SmithE.M. NajumudeenA.K. GilroyK. RidgwayR.A. FlanaganD.J. SmithR.C.L. McDonaldL. MacKayC. CheastyA. McArthurK. StanwayE. LeachJ.D. JackstadtR. WaldronJ.A. CampbellA.D. VlachogiannisG. ValeriN. HaigisK.M. SonenbergN. ProudC.G. JonesN.P. SwarbrickM.E. McKinnonH.J. FallerW.J. Le QuesneJ. EdwardsJ. WillisA.E. BushellM. SansomO.J. MNK inhibition sensitizes KRAS -mutant colorectal cancer to MTORC1 inhibition by reducing eIF4E Phosphorylation and c-MYC expression.Cancer Discov.20211151228124710.1158/2159‑8290.CD‑20‑065233328217
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673260837231120101508
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MNK: A Novel Promising Target for Cancer Immunotherapy
Curr. Med. Chem. 32, 3347 (2025); https://doi.org/10.2174/0109298673260837231120101508
/content/journals/cmc/10.2174/0109298673260837231120101508
/content/journals/cmc/10.2174/0109298673260837231120101508
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  • Article Type:     Review Article
Keyword(s): cancer therapy; immunotherapy; MAPK; MNK; novel target; promising target

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