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2000
Volume 20, Issue 2
  • ISSN: 1574-8928
  • E-ISSN: 2212-3970

Abstract

Selinexor treats lung cancer, particularly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This review summarizes the prevalence and types of lung cancer and emphasizes the challenges associated with current treatments like resistance and limited effectiveness. Selinexor is a selective inhibitor of nuclear export (SINE) that has emerged as a potential therapy that targets the nuclear export of tumor suppressor proteins. The mechanisms of selinexor, its potential in combination therapies, and challenges like side effects and drug resistance are explained in this review. Key findings highlight the effectiveness of selinexor in preclinical studies, particularly against KRAS-mutant NSCLC and in combination with chemotherapy for SCLC. The review concludes with a discussion of future directions and underscores the potential of selinexor to improve the treatment strategies for lung cancer.

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2025-09-04

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References

  1. LeiterA. VeluswamyR.R. WisniveskyJ.P. The global burden of lung cancer: current status and future trends.Nat. Rev. Clin. Oncol.202320962463910.1038/s41571‑023‑00798‑337479810
     [Google Scholar]
  2. BartaJ.A. PowellC.A. WisniveskyJ.P. Global epidemiology of lung cancer.Ann. Glob. Health2019851810.5334/aogh.241930741509
     [Google Scholar]
  3. XiaoY. LiuP. WeiJ. ZhangX. GuoJ. LinY. Recent progress in targeted therapy for non-small cell lung cancer.Front. Pharmacol.202314112554710.3389/fphar.2023.112554736909198
     [Google Scholar]
  4. RudinC.M. IsmailaN. HannC.L. MalhotraN. MovsasB. NorrisK. PietanzaM.C. RamalingamS.S. TurrisiA.T.III GiacconeG. Treatment of small-cell lung cancer: American society of clinical oncology endorsement of the american college of chest physicians guideline.J. Clin. Oncol.201533344106411110.1200/JCO.2015.63.791826351333
     [Google Scholar]
  5. ByersL.A. RudinC.M. Small cell lung cancer: Where do we go from here?Cancer2015121566467210.1002/cncr.2909825336398
     [Google Scholar]
  6. RanganathanP. KashyapT. YuX. MengX. LaiT.H. McNeilB. BhatnagarB. ShachamS. KauffmanM. DorranceA.M. BlumW. SampathD. LandesmanY. GarzonR. XPO1 inhibition using selinexor synergizes with chemotherapy in acute myeloid leukemia by targeting DNA repair and restoring topoisomerase iiα to the nucleus.Clin. Cancer Res.201622246142615210.1158/1078‑0432.CCR‑15‑288527358488
     [Google Scholar]
  7. KashyapT. ArguetaC. UngerT. KlebanovB. DeblerS. SenapedisW. CrochiereM.L. LeeM.S. KauffmanM. ShachamS. LandesmanY. Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents.Oncotarget2018956307733078610.18632/oncotarget.2563730112106
     [Google Scholar]
  8. Quintanal-VillalongaA. TaniguchiH. HaoY. ChowA. ZhanY.A. ChavanS.S. UddinF. AllajV. ManojP. ShahN.S. ChanJ.M. OffinM. CiampricottiM. Ray-KirtonJ. EggerJ. BhanotU. LinkovI. AsherM. RoehrlM.H. QiuJ. de StanchinaE. HollmannT.J. KocheR.P. SenT. PoirierJ.T. RudinC.M. Inhibition of XPO1 sensitizes small cell lung cancer to first- and second-line chemotherapy.Cancer Res.202282347248310.1158/0008‑5472.CAN‑21‑296434815254
     [Google Scholar]
  9. LandesJ.R. MooreS.A. BartleyB.R. DoanH.Q. RadyP.L. TyringS.K. The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: A comprehensive review.J. Cancer Res. Clin. Oncol.202314952139215510.1007/s00432‑022‑04247‑z35941226
     [Google Scholar]
  10. Eutectic form of Selinexor.Patent CN 113423468 A,2020
  11. Preparation method of Selinexor and its intermediates. Patent US 9079865 B2,2015
  12. Preparation method of Selinexor and its intermediates.Patent CN 112679477 B,2020
  13. MeissnerT. KrauseE. VinkemeierU. Ratjadone and leptomycin B block CRM1‐dependent nuclear export by identical mechanisms.FEBS Lett.20045761-2273010.1016/j.febslet.2004.08.05615474004
     [Google Scholar]
  14. FukudaM. AsanoS. NakamuraT. AdachiM. YoshidaM. YanagidaM. NishidaE. CRM1 is responsible for intracellular transport mediated by the nuclear export signal.Nature1997390665730831110.1038/368949384386
     [Google Scholar]
  15. HuttenS. KehlenbachR.H. CRM1-mediated nuclear export: To the pore and beyond.Trends Cell Biol.201717419320110.1016/j.tcb.2007.02.003
     [Google Scholar]
  16. Gupta A. SaltarskiJ.M Therapeutic Targeting of Nuclear Export Inhibition in Lung Cancer.J Thorac Oncol.2017121446145010.1016/j.tcb.2007.02.003
     [Google Scholar]
  17. GaoW. LuC. ChenL. KeohavongP. Overexpression of CRM1: A characteristic feature in a transformed phenotype of lung carcinogenesis and a molecular target for lung cancer adjuvant therapy.J. Thorac. Oncol.201510581582510.1097/JTO.000000000000048525629636
     [Google Scholar]
  18. NagasakaM. AsadM.F.B. Al HallakM.N. UddinM.H. SukariA. BacaY. XiuJ. MageeD. MamdaniH. UpretyD. KimC. XiaB. LiuS.V. NievaJ.J. LopesG. BeplerG. BorghaeiH. DemeureM.J. RaezL.E. MaP.C. PuriS. KornW.M. AzmiA.S. Impact of XPO1 mutations on survival outcomes in metastatic non-small cell lung cancer (NSCLC).Lung Cancer2021160929810.1016/j.lungcan.2021.08.01034482103
     [Google Scholar]
  19. KhanH.Y. NagasakaM. LiY. AboukameelA. UddinM.H. SextonR. BannouraS. MzannarY. Al-HallakM.N. KimS. BeydounR. LandesmanY. MamdaniH. UpretyD. PhilipP.A. MohammadR.M. ShieldsA.F. AzmiA.S. Inhibitor of the nuclear transport protein XPO1 enhances the anticancer efficacy of KRAS G12C inhibitors in preclinical models of KRAS G12C–mutant cancers.Cancers. Cancer Res Commun.20222534235210.1158/2767‑9764.CRC‑21‑017635573474
     [Google Scholar]
  20. RosenJ.C. WeissJ. PhamN.A. LiQ. Martins-FilhoS.N. WangY. TsaoM.S. MoghalN. Antitumor efficacy of XPO1 inhibitor Selinexor in KRAS-mutant lung adenocarcinoma patient-derived xenografts.Transl. Oncol.2021141010117910.1016/j.tranon.2021.10117934284202
     [Google Scholar]
  21. HerdeisL. GerlachD. McConnellD.B. KesslerD. Stopping the beating heart of cancer: KRAS reviewed.Curr. Opin. Struct. Biol.20217113614710.1016/j.sbi.2021.06.01334303932
     [Google Scholar]
  22. Molina-ArcasM. SamaniA. DownwardJ. Drugging the undruggable: Advances on RAS targeting in cancer.Genes (Basel)202112689910.3390/genes1206089934200676
     [Google Scholar]
  23. MatikasA. MistriotisD. GeorgouliasV. KotsakisA. Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity.Crit. Rev. Oncol. Hematol.201711011210.1016/j.critrevonc.2016.12.00528109399
     [Google Scholar]
  24. KimJ. McMillanE. KimH.S. VenkateswaranN. MakkarG. Rodriguez-CanalesJ. VillalobosP. NeggersJ.E. MendirattaS. WeiS. LandesmanY. SenapedisW. BalogluE. ChowC.W.B. FrinkR.E. GaoB. RothM. MinnaJ.D. DaelemansD. WistubaI.I. PosnerB.A. ScaglioniP.P. WhiteM.A. XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer.Nature2016538762311411710.1038/nature1977127680702
     [Google Scholar]
  25. PolinaV. Clinical CDK2 Inhibitors: Trends to Selectivity and Efficacy.Recent Pat Anticancer Drug Discov.202218210210710.3390/genes12060899
     [Google Scholar]
  26. ZhuZ.C. LiuJ.W. YangC. ZhaoM. XiongZ.Q. XPO1 inhibitor KPT-330 synergizes with Bcl-xL inhibitor to induce cancer cell apoptosis by perturbing rRNA processing and Mcl-1 protein synthesis.Cell Death Dis.201910639510.1038/s41419‑019‑1627‑931113936
     [Google Scholar]
  27. BarretinaJ. CaponigroG. StranskyN. VenkatesanK. MargolinA.A. KimS. WilsonC.J. LehárJ. KryukovG.V. SonkinD. ReddyA. LiuM. MurrayL. BergerM.F. MonahanJ.E. MoraisP. MeltzerJ. KorejwaA. Jané-ValbuenaJ. MapaF.A. ThibaultJ. Bric-FurlongE. RamanP. ShipwayA. EngelsI.H. ChengJ. YuG.K. YuJ. AspesiP.Jr de SilvaM. JagtapK. JonesM.D. WangL. HattonC. PalescandoloE. GuptaS. MahanS. SougnezC. OnofrioR.C. LiefeldT. MacConaillL. WincklerW. ReichM. LiN. MesirovJ.P. GabrielS.B. GetzG. ArdlieK. ChanV. MyerV.E. WeberB.L. PorterJ. WarmuthM. FinanP. HarrisJ.L. MeyersonM. GolubT.R. MorrisseyM.P. SellersW.R. SchlegelR. GarrawayL.A. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity.Nature2012483739160360710.1038/nature1100322460905
     [Google Scholar]
  28. AzizianN.G. LiY. XPO1-dependent nuclear export as a target for cancer therapy.J. Hematol. Oncol.20201316110.1186/s13045‑020‑00903‑432487143
     [Google Scholar]
  29. CeramiE. GaoJ. DogrusozU. GrossB.E. SumerS.O. AksoyB.A. JacobsenA. ByrneC.J. HeuerM.L. LarssonE. AntipinY. RevaB. GoldbergA.P. SanderC. SchultzN. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data.Cancer Discov.20122540140410.1158/2159‑8290.CD‑12‑009522588877
     [Google Scholar]
  30. IrelandA.S. MicinskiA.M. KastnerD.W. GuoB. WaitS.J. SpainhowerK.B. ConleyC.C. ChenO.S. GuthrieM.R. SolteroD. QiaoY. HuangX. TarapcsákS. DevarakondaS. ChalishazarM.D. GertzJ. MoserJ.C. MarthG. PuriS. WittB.L. SpikeB.T. OliverT.G. MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate.Cancer Cell2020381607810.1016/j.ccell.2020.05.00132473656
     [Google Scholar]
  31. AugertA. MathsyarajaH. IbrahimA.H. FreieB. GeuenichM.J. ChengP.F. AlibeckoffS.P. WuN. HiattJ.B. BasomR. GazdarA. SullivanL.B. EisenmanR.N. MacPhersonD. MAX functions as a tumor suppressor and rewires metabolism in small cell lung cancer.Cancer Cell20203819711410.1016/j.ccell.2020.04.01632470392
     [Google Scholar]
  32. El-DeiryW.S. TokinoT. VelculescuV.E. LevyD.B. ParsonsR. TrentJ.M. LinD. MercerW.E. KinzlerK.W. VogelsteinB. WAF1, a potential mediator of p53 tumor suppression.Cell199375481782510.1016/0092‑8674(93)90500‑P8242752
     [Google Scholar]
  33. FarmerH. McCabeN. LordC.J. TuttA.N.J. JohnsonD.A. RichardsonT.B. SantarosaM. DillonK.J. HicksonI. KnightsC. MartinN.M.B. JacksonS.P. SmithG.C.M. AshworthA. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature2005434703591792110.1038/nature0344515829967
     [Google Scholar]
  34. McCabeN. TurnerN.C. LordC.J. KluzekK. BiałkowskaA. SwiftS. GiavaraS. O’ConnorM.J. TuttA.N. ZdzienickaM.Z. SmithG.C.M. AshworthA. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition.Cancer Res.200666168109811510.1158/0008‑5472.CAN‑06‑014016912188
     [Google Scholar]
  35. ByersL.A. WangJ. NilssonM.B. FujimotoJ. SaintignyP. YordyJ. GiriU. PeytonM. FanY.H. DiaoL. MasrorpourF. ShenL. LiuW. DuchemannB. TumulaP. BhardwajV. WelshJ. WeberS. GlissonB.S. KalhorN. WistubaI.I. GirardL. LippmanS.M. MillsG.B. CoombesK.R. WeinsteinJ.N. MinnaJ.D. HeymachJ.V. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1.Cancer Discov.20122979881110.1158/2159‑8290.CD‑12‑011222961666
     [Google Scholar]
  36. WeaverA.N. YangE.S. Beyond DNA repair: Additional functions of PARP-1 in cancer.Front. Oncol.2013329010.3389/fonc.2013.0029024350055
     [Google Scholar]
  37. HussainM. MateoJ. FizaziK. SaadF. ShoreN. SandhuS. ChiK.N. SartorO. AgarwalN. OlmosD. Thiery-VuilleminA. TwardowskiP. RoubaudG. ÖzgüroğluM. KangJ. BurgentsJ. GrestyC. CorcoranC. AdelmanC.A. de BonoJ. PROfound Trial Investigators Survival with olaparib in metastatic castration-resistant prostate cancer.N. Engl. J. Med.2020383242345235710.1056/NEJMoa202248532955174
     [Google Scholar]
  38. de BonoJ. RamanathanR.K. MinaL. ChughR. GlaspyJ. RafiiS. KayeS. SachdevJ. HeymachJ. SmithD.C. HenshawJ.W. HerriottA. PattersonM. CurtinN.J. ByersL.A. WainbergZ.A. Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers.Cancer Discov.20177662062910.1158/2159‑8290.CD‑16‑125028242752
     [Google Scholar]
  39. AtrafiF. GroenH.J.M. ByersL.A. GarraldaE. LolkemaM.P. SanghaR.S. ViteriS. ChaeY.K. CamidgeD.R. GabrailN.Y. HuB. TianT. NuthalapatiS. HoeningE. HeL. KomarnitskyP. CallesA. A phase i dose-escalation study of veliparib combined with carboplatin and etoposide in patients with extensive-stage small cell lung cancer and other solid tumors.Clin. Cancer Res.201925249650510.1158/1078‑0432.CCR‑18‑201430327308
     [Google Scholar]
  40. BuontempoF. ChiariniF. BressaninD. TabelliniG. MelchiondaF. PessionA. FiniM. NeriL.M. McCubreyJ.A. MartelliA.M. Activity of the selective IκB kinase inhibitor BMS-345541 against T-cell acute lymphoblastic leukemia.Cell Cycle201211132467247510.4161/cc.2085922713244
     [Google Scholar]
  41. AllenJ.E. KrigsfeldG. MayesP.A. PatelL. DickerD.T. PatelA.S. DolloffN.G. MessarisE. ScataK.A. WangW. ZhouJ.Y. WuG.S. El-DeiryW.S. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.Sci. Transl. Med.20135171171ra1710.1126/scitranslmed.300482823390247
     [Google Scholar]
  42. LalloA. FreseK.K. MorrowC.J. SloaneR. GulatiS. SchenkM.W. TrapaniF. SimmsN. GalvinM. BrownS. HodgkinsonC.L. PriestL. HughesA. LaiZ. CadoganE. KhandelwalG. SimpsonK.L. MillerC. BlackhallF. O’ConnorM.J. DiveC. The combination of the parp inhibitor olaparib and the WEE1 inhibitor AZD1775 as a new therapeutic option for small cell lung cancer.Clin. Cancer Res.201824205153516410.1158/1078‑0432.CCR‑17‑280529941481
     [Google Scholar]
  43. BalajiK. VijayaraghavanS. DiaoL. TongP. FanY. CareyJ.P.W. BuiT.N. WarnerS. HeymachJ.V. HuntK.K. WangJ. ByersL.A. KeyomarsiK. AXL inhibition suppresses the dna damage response and sensitizes cells to PARP inhibition in multiple cancers.Mol. Cancer Res.2017151455810.1158/1541‑7786.MCR‑16‑015727671334
     [Google Scholar]
  44. CardnellR.J. FengY. DiaoL. FanY.H. MasrorpourF. WangJ. ShenY. MillsG.B. MinnaJ.D. HeymachJ.V. ByersL.A. Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer.Clin. Cancer Res.201319226322632810.1158/1078‑0432.CCR‑13‑197524077350
     [Google Scholar]
  45. CardnellR.J. FengY. MukherjeeS. DiaoL. TongP. StewartC.A. MasrorpourF. FanY. NilssonM. ShenY. HeymachJ.V. WangJ. ByersL.A. Activation of the PI3K/mTOR Pathway following PARP inhibition in small cell lung cancer.PLoS One2016114e015258410.1371/journal.pone.015258427055253
     [Google Scholar]
  46. ChowdhuryP. DeyP. GhoshS. SarmaA. GhoshU. Reduction of metastatic potential by inhibiting EGFR/Akt/p38/ERK signaling pathway and epithelial-mesenchymal transition after carbon ion exposure is potentiated by PARP-1 inhibition in non-small-cell lung cancer.BMC Cancer201919182910.1186/s12885‑019‑6015‑431438892
     [Google Scholar]
  47. TsaiW.B. ChungY.M. TakahashiY. XuZ. HuM.C.T. Functional interaction between FOXO3a and ATM regulates DNA damage response.Nat. Cell Biol.200810446046710.1038/ncb170918344987
     [Google Scholar]
  48. WangJ. SunT. MengZ. WangL. LiM. ChenJ. QinT. YuJ. ZhangM. BieZ. DongZ. JiangX. LinL. ZhangC. LiuZ. JiangR. YangG. LiL. ZhangY. HuangD. XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a.Cancer Lett.202150319721210.1016/j.canlet.2021.01.00833493586
     [Google Scholar]
  49. SunL. GaoL. ZhaoY. WangY. XuQ. ZhengY. ChenJ. WangH. WangL. Understanding and targeting the epigenetic regulation to overcome EGFR-TKIs resistance in human cancer.Recent Patents Anticancer Drug Discov.202318450651610.2174/157489281866622120114581036464873
     [Google Scholar]
  50. MarcouxN. GettingerS.N. O’KaneG. ArbourK.C. NealJ.W. HusainH. EvansT.L. BrahmerJ.R. MuzikanskyA. BonomiP.D. del PreteS. WurtzA. FaragoA.F. Dias-SantagataD. Mino-KenudsonM. ReckampK.L. YuH.A. WakeleeH.A. ShepherdF.A. PiotrowskaZ. SequistL.V. EGFR -mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes.J. Clin. Oncol.201937427828510.1200/JCO.18.0158530550363
     [Google Scholar]
  51. AggarwalR. HuangJ. AlumkalJ.J. ZhangL. FengF.Y. ThomasG.V. WeinsteinA.S. FriedlV. ZhangC. WitteO.N. LloydP. GleaveM. EvansC.P. YoungrenJ. BeerT.M. RettigM. WongC.K. TrueL. FoyeA. PlaydleD. RyanC.J. LaraP. ChiK.N. UzunangelovV. SokolovA. NewtonY. BeltranH. DemichelisF. RubinM.A. StuartJ.M. SmallE.J. Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study.J. Clin. Oncol.201836242492250310.1200/JCO.2017.77.688029985747
     [Google Scholar]
  52. OffinM. ChanJ.M. TenetM. RizviH.A. ShenR. RielyG.J. RekhtmanN. DaneshbodY. Quintanal-VillalongaA. PensonA. HellmannM.D. ArcilaM.E. LadanyiM. Pe’erD. KrisM.G. RudinC.M. YuH.A. Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes.J. Thorac. Oncol.201914101784179310.1016/j.jtho.2019.06.00231228622
     [Google Scholar]
  53. RudinC.M. BrambillaE. Faivre-FinnC. SageJ. Small-cell lung cancer.Nat. Rev. Dis. Primers202171310.1038/s41572‑020‑00235‑033446664
     [Google Scholar]
  54. GeorgeJ. LimJ.S. JangS.J. CunY. OzretićL. KongG. LeendersF. LuX. Fernández-CuestaL. BoscoG. MüllerC. DahmenI. JahchanN.S. ParkK.S. YangD. KarnezisA.N. VakaD. TorresA. WangM.S. KorbelJ.O. MenonR. ChunS.M. KimD. WilkersonM. HayesN. EngelmannD. PützerB. BosM. MichelsS. VlasicI. SeidelD. PintherB. SchaubP. BeckerC. AltmüllerJ. YokotaJ. KohnoT. IwakawaR. TsutaK. NoguchiM. MuleyT. HoffmannH. SchnabelP.A. PetersenI. ChenY. SoltermannA. TischlerV. ChoiC. KimY.H. MassionP.P. ZouY. JovanovicD. KonticM. WrightG.M. RussellP.A. SolomonB. KochI. LindnerM. MuscarellaL.A. la TorreA. FieldJ.K. JakopovicM. KnezevicJ. Castaños-VélezE. RozL. PastorinoU. BrustugunO.T. Lund-IversenM. ThunnissenE. KöhlerJ. SchulerM. BotlingJ. SandelinM. Sanchez-CespedesM. SalvesenH.B. AchterV. LangU. BogusM. SchneiderP.M. ZanderT. AnsénS. HallekM. WolfJ. VingronM. YatabeY. TravisW.D. NürnbergP. ReinhardtC. PernerS. HeukampL. BüttnerR. HaasS.A. BrambillaE. PeiferM. SageJ. ThomasR.K. Comprehensive genomic profiles of small cell lung cancer.Nature20155247563475310.1038/nature1466426168399
     [Google Scholar]
  55. NiederstM.J. SequistL.V. PoirierJ.T. MermelC.H. LockermanE.L. GarciaA.R. KatayamaR. CostaC. RossK.N. MoranT. HoweE. FultonL.E. MulveyH.E. BernardoL.A. MohamoudF. MiyoshiN. VanderLaanP.A. CostaD.B. JänneP.A. BorgerD.R. RamaswamyS. ShiodaT. IafrateA.J. GetzG. RudinC.M. Mino-KenudsonM. EngelmanJ.A. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer.Nat. Commun.201561637710.1038/ncomms737725758528
     [Google Scholar]
  56. Quintanal-VillalongaA. DuraniV. SabetA. RedinE. KawasakiK. ShaferM. KarthausW.R. ZaidiS. ZhanY.A. ManojP. SridharH. ShahN.S. ChowA. BhanotU.K. LinkovI. AsherM. YuH.A. QiuJ. de StanchinaE. PatelR.A. MorrisseyC. HaffnerM.C. KocheR.P. SawyersC.L. RudinC.M. Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers.Sci. Transl. Med.202315707eadf700610.1126/scitranslmed.adf700637531417
     [Google Scholar]
  57. AltanM. TuJ. MiltonD.R. YilmazB. TianY. FossellaF.V. MottF.E. BlumenscheinG.R. StephenB. KarpD.D. Meric-BernstamF. HeymachJ.V. NaingA. Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non–small cell lung cancer.Cancer2023129172685269310.1002/cncr.3482037129197
     [Google Scholar]
  58. MuiC.W. ChanW.N. ChenB. CheungA.H.K. YuJ. LoK.W. KeH. KangW. ToK.F. Targeting YAP1 / TAZ in nonsmall‐cell lung carcinoma: From molecular mechanisms to precision medicine.Int. J. Cancer2023152455857110.1002/ijc.3424935983734
     [Google Scholar]
  59. MartinA.P.J. AushevV.N. ZalcmanG. CamonisJ.H. The STK38–XPO1 axis, a new actor in physiology and cancer.Cell. Mol. Life Sci.20217851943195510.1007/s00018‑020‑03690‑w33145612
     [Google Scholar]
  60. SharmaU. TuliH.S. UttamV. ChoudharyR. SharmaB. SharmaU. PrakashH. JainA. Role of Hedgehog and Hippo signaling pathways in cancer: A special focus on non-coding RNAs.Pharmacol. Res.202218610652310.1016/j.phrs.2022.10652336377125
     [Google Scholar]
  61. CuiY. LiY. JiJ. HuN. MinK. YingW. FanL. HongM. LiJ. SunZ. QuX. Dynamic single-cell RNA-Seq reveals mechanism of selinexor-resistance in chronic myeloid leukemia.Int. Immunopharmacol.202413411221210.1016/j.intimp.2024.11221238728882
     [Google Scholar]
  62. YunC.W. KimH.J. LimJ.H. LeeS.H. Heat shock proteins: Agents of cancer development and therapeutic targets in anti-cancer therapy.Cells2019916010.3390/cells901006031878360
     [Google Scholar]
  63. ShridharV. BibleK.C. StaubJ. AvulaR. LeeY.K. KalliK. HuangH. HartmannL.C. KaufmannS.H. SmithD.I. Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer.Cancer Res.200161104258426511358853
     [Google Scholar]
  64. ChenX. DongX.S. GaoH.Y. JiangY.F. JinY.L. ChangY.Y. ChenL.Y. WangJ.H. Suppression of HSP27 increases the anti-tumor effects of quercetin in human leukemia U937 cells.Mol. Med. Rep.201613168969610.3892/mmr.2015.460026648539
     [Google Scholar]
  65. LeiG. ZhuangL. GanB. Targeting ferroptosis as a vulnerability in cancer.Nat. Rev. Cancer202222738139610.1038/s41568‑022‑00459‑035338310
     [Google Scholar]
  66. FuD. WangC. YuL. YuR. Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling.Cell. Mol. Biol. Lett.20212612610.1186/s11658‑021‑00271‑y34098867
     [Google Scholar]
  67. ChenT.C. ChuangJ.Y. KoC.Y. KaoT.J. YangP.Y. YuC.H. LiuM.S. HuS.L. TsaiY.T. ChanH. ChangW.C. HsuT.I. AR ubiquitination induced by the curcumin analog suppresses growth of temozolomide-resistant glioblastoma through disrupting GPX4-Mediated redox homeostasis.Redox Biol.20203010141310.1016/j.redox.2019.10141331896509
     [Google Scholar]
  68. ChenP. LiX. ZhangR. LiuS. XiangY. ZhangM. ChenX. PanT. YanL. FengJ. DuanT. WangD. ChenB. JinT. WangW. ChenL. HuangX. ZhangW. SunY. LiG. KongL. ChenX. LiY. YangZ. ZhangQ. ZhuoL. SuiX. XieT. Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation.Theranostics202010115107511910.7150/thno.4470532308771
     [Google Scholar]
  69. TangD. KroemerG. Ferroptosis.Curr. Biol.20203021R1292R129710.1016/j.cub.2020.09.06833142092
     [Google Scholar]
  70. BlairI. FanJ. GillespieK. MesarosC. Ferroptosis and HMGB2 induced calreticulin translocation required for immunogenic cell death are controlled by the nuclear exporter XPO1. Res SqRes Sq2024rs.3rs400945910.21203/rs.3.rs‑4009459/v1
     [Google Scholar]
  71. GillespieK.P. PirnieR. MesarosC. BlairI.A. Cisplatin Dependent Secretion of Immunomodulatory High Mobility Group Box 1 (HMGB1) Protein from Lung Cancer Cells.Biomolecules2023139133510.3390/biom1309133537759736
     [Google Scholar]
  72. StarkovaT. PolyanichkoA. TomilinA.N. ChikhirzhinaE. Structure and functions of HMGB2 protein.Int. J. Mol. Sci.2023249833410.3390/ijms2409833437176041
     [Google Scholar]
  73. SprootenJ. LaureanoR.S. VanmeerbeekI. GovaertsJ. NaulaertsS. BorrasD.M. KingetL. FucíkováJ. ŠpíšekR. JelínkováL.P. KeppO. KroemerG. KryskoD.V. CoosemansA. VaesR.D.W. De RuysscherD. De VleeschouwerS. WautersE. SmitsE. TejparS. BeuselinckB. HatseS. WildiersH. ClementP.M. VandenabeeleP. ZitvogelL. GargA.D. Trial watch: Chemotherapy-induced immunogenic cell death in oncology.OncoImmunology2023121221959110.1080/2162402X.2023.221959137284695
     [Google Scholar]
  74. XieX. LeeJ. LiuH. PearsonT. LuA.Y. TripathyD. DeviG.R. BartholomeuszC. UenoN.T. Birinapant enhances gemcitabine’s antitumor efficacy in triple-negative breast cancer by inducing intrinsic pathway–dependent apoptosis.Mol. Cancer Ther.202120229630610.1158/1535‑7163.MCT‑19‑116033323457
     [Google Scholar]
  75. ArangoN.P. YucaE. ZhaoM. EvansK.W. ScottS. KimC. Gonzalez-AnguloA.M. JankuF. UenoN.T. TripathyD. AkcakanatA. NaingA. Meric-BernstamF. Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer.Breast Cancer Res.201719193, 19, 9310.1186/s13058‑017‑0878‑628810913
     [Google Scholar]
  76. HandleyK.F. Rodriguez-AguayoC. MaS. SturE. JosephR. BayraktarE. DasariS.K. NguyenN. PowellR.T. SobieskiM. IvanC. KimM. UmamaheswaranS. GlassmanD. WenY. AmeroP. StephanC. ColemanR.L. LandesmanY. WestinS.N. RamP.T. SoodA.K. Rational combination of CRM1 inhibitor selinexor and olaparib shows synergy in ovarian cancer cell lines and mouse models.Mol. Cancer Ther.202120122352236110.1158/1535‑7163.MCT‑21‑037034583979
     [Google Scholar]
  77. van der WattP.J. MaskeC.P. HendricksD.T. ParkerM.I. DennyL. GovenderD. BirrerM.J. LeanerV.D. The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.Int. J. Cancer200912481829184010.1002/ijc.2414619117056
     [Google Scholar]
  78. XiaL. WangM. LiH. TangX. ChenF. CuiJ. The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology.Cancer Med.2018773393340510.1002/cam4.159229797792
     [Google Scholar]
  79. SongG. RenJ. LiY. CuiJ. Interference with XPO1 suppresses the stemness and radioresistance of CD44 positive cervical cancer cells via binding with Rad21.Ann. Clin. Lab. Sci.202353227829237094850
     [Google Scholar]
  80. DelmanM. AvcıS.T. Akçokİ. KanburT. ErdalE. ÇağırA. Antiproliferative activity of (R)-4′-methylklavuzon on hepatocellular carcinoma cells and EpCAM+/CD133+ cancer stem cells via SIRT1 and Exportin-1 (CRM1) inhibition.Eur. J. Med. Chem.201918018022423710.1016/j.ejmech.2019.07.02431306909
     [Google Scholar]
  81. UddinM.H. Al-HallakM.N. KhanH.Y. AboukameelA. LiY. BannouraS.F. DysonG. KimS. MzannarY. AzarI. OdishoT. MohamedA. LandesmanY. KimS. BeydounR. MohammadR.M. PhilipP.A. ShieldsA.F. AzmiA.S. Molecular analysis of XPO1 inhibitor and gemcitabine–nab‐paclitaxel combination in KPC pancreatic cancer mouse model.Clin. Transl. Med.20231312e151310.1002/ctm2.151338131168
     [Google Scholar]
  82. AzmiA.S. KhanH.Y. MuqbilI. AboukameelA. NeggersJ.E. DaelemansD. MahipalA. DysonG. KamgarM. Al-HallakM.N. TesfayeA. KimS. ShidhamV. M MohammadR. PhilipP.A. Preclinical assessment with clinical validation of selinexor with gemcitabine and nab-paclitaxel for the treatment of pancreatic ductal adenocarcinoma.Clin. Cancer Res.20202661338134810.1158/1078‑0432.CCR‑19‑172831831564
     [Google Scholar]
  83. WangZ. PanB. YaoY. QiuJ. ZhangX. WuX. TangN. XPO1 intensifies sorafenib resistance by stabilizing acetylation of NPM1 and enhancing epithelial-mesenchymal transition in hepatocellular carcinoma.Biomed. Pharmacother.202316011440210.1016/j.biopha.2023.11440236791564
     [Google Scholar]
  84. ZhouJ.N. ZengQ. WangH.Y. ZhangB. LiS.T. NanX. CaoN. FuC.J. YanX.L. JiaY.L. WangJ.X. ZhaoA.H. LiZ.W. LiY.H. XieX.Y. ZhangX.M. DongY. XuY.C. HeL.J. YueW. PeiX.T. MicroRNA‐125b attenuates epithelial‐mesenchymal transitions and targets stem‐like liver cancer cells through small mothers against decapentaplegic 2 and 4.Hepatology201562380181510.1002/hep.2788725953743
     [Google Scholar]
  85. WahbaA. RathB.H. O’NeillJ.W. CamphausenK. TofilonP.J. The XPO1 inhibitor selinexor inhibits translation and enhances the radiosensitivity of glioblastoma cells grown In Vitro and In Vivo.Mol. Cancer Ther.20181781717172610.1158/1535‑7163.MCT‑17‑130329866745
     [Google Scholar]
  86. ZhaoK. BraunM. MeyerL. OtteK. RaiferH. HelmprobstF. MöschlV. PagenstecherA. UrbanH. RonellenfitschM.W. SteinbachJ.P. PesekJ. WatzerB. NockherW.A. TaudteR.V. NeubauerA. NimskyC. BartschJ.W. RuschT. A novel approach for glioblastoma treatment by combining apoptosis inducers (TMZ, MTX, and Cytarabine) with E.V.A. (Eltanexor, Venetoclax, and A1210477) inhibiting XPO1, Bcl-2, and Mcl-1.Cells2024137632, 13, 63210.3390/cells1307063238607071
     [Google Scholar]
  87. CastellóA. IzquierdoJ.M. WelnowskaE. CarrascoL. RNA nuclear export is blocked by poliovirus 2A protease and is concomitant with nucleoporin cleavage.J. Cell Sci.2009122203799380910.1242/jcs.05598819789179
     [Google Scholar]
  88. TabeY. KojimaK. YamamotoS. SekiharaK. MatsushitaH. DavisRE. Ribosomal biogenesis and translational flux inhibition by the selective inhibitor of nuclear export (SINE) XPO1 antagonist KPT-185PLoS One.2015109e013721010.1371/journal.pone.0137210
     [Google Scholar]
  89. YangX.Z. ChengT.T. HeQ.J. LeiZ.Y. ChiJ. TangZ. LiaoQ.X. ZhangH. ZengL.S. CuiS.Z. LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway.Mol. Cancer201817112610.1186/s12943‑018‑0874‑130134915
     [Google Scholar]
  90. LvC. LiF. LiX. MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.Nat Commun.201781103610.1038/s41467‑017‑01059‑5
     [Google Scholar]
  91. CleversH. LohK.M. NusseR. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control.Science20143466205124801210.1126/science.124801225278615
     [Google Scholar]
  92. ReyesM. FloresT. BetancurD. Peña-OyarzúnD. TorresV.A. Wnt/β-catenin signaling in oral carcinogenesis.Int. J. Mol. Sci.20202113468210.3390/ijms2113468232630122
     [Google Scholar]
  93. LiuJ. XiaoQ. XiaoJ. NiuC. LiY. ZhangX. ZhouZ. ShuG. YinG. Wnt/β-catenin signalling: Function, biological mechanisms, and therapeutic opportunities.Signal Transduct. Target. Ther.202271310.1038/s41392‑021‑00762‑634980884
     [Google Scholar]
  94. PaiS.G. CarneiroB.A. MotaJ.M. CostaR. LeiteC.A. Barroso-SousaR. KaplanJ.B. ChaeY.K. GilesF.J. Wnt/beta-catenin pathway: Modulating anticancer immune response.J. Hematol. Oncol.201710110110.1186/s13045‑017‑0471‑628476164
     [Google Scholar]
  95. WallJ.A. Meza-PerezS. ScaliseC.B. KatreA. LondoñoA.I. TurbittW.J. RandallT. NorianL.A. ArendR.C. Manipulating the Wnt/β-catenin signaling pathway to promote anti-tumor immune infiltration into the TME to sensitize ovarian cancer to ICB therapy.Gynecol. Oncol.2021160128529410.1016/j.ygyno.2020.10.03133168307
     [Google Scholar]
  96. CuiC. ZhouX. ZhangW. QuY. KeX. Is β-Catenin a Druggable Target for Cancer Therapy?Trends Biochem. Sci.201843862363410.1016/j.tibs.2018.06.00330056837
     [Google Scholar]
  97. KimW.K. BuckleyA.J. LeeD.H. HirotoA. NenningerC.H. OlsonA.W. WangJ. LiZ. VikramR. AdzavonY.M. YauT. BaoY. KahnM. GeradtsJ. XiaoG.Q. SunZ. Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation.Nat. Commun.2024151123110.1038/s41467‑024‑45489‑438336745
     [Google Scholar]
  98. MahipalA. MalafaM. Importins and exportins as therapeutic targets in cancer.Pharmacol. Ther.201616413514310.1016/j.pharmthera.2016.03.02027113410
     [Google Scholar]
  99. SakumaS. RaicesM. BorlidoJ. GuglielmiV. ZhuE.Y.S. D’AngeloM.A. Inhibition of nuclear pore complex formation selectively induces cancer cell death.Cancer Discov.202111117619310.1158/2159‑8290.CD‑20‑058132988961
     [Google Scholar]
/content/journals/pra/10.2174/0115748928322627241016120142
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Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies
Recent Patents on Anti-Cancer Drug Discovery 20, 274 (2025); https://doi.org/10.2174/0115748928322627241016120142
/content/journals/pra/10.2174/0115748928322627241016120142
/content/journals/pra/10.2174/0115748928322627241016120142
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  • Article Type:     Review Article
Keyword(s): lung cancer; NSCLC; SCLC; Selinexor; SINE; XPO1

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