Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Medicinal Chemistry
  4. Volume 32, Issue 3
  5. Article
Volume 32, Issue 3
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered “undruggable” due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673269305231115102542
2024-01-15
2025-01-17

  • From This Site

    /content/journals/cmc/10.2174/0109298673269305231115102542
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Castañeda-GonzálezJ.P. ChavesJ.J. Parra-MedinaR. Multiple mutations in the EGFR gene in lung cancer: A systematic review.Transl. Lung Cancer Res.202211102148216310.21037/tlcr‑22‑23536386461
     [Google Scholar]
  2. MitsudomiT. YatabeY. Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer.Cancer Sci.200798121817182410.1111/j.1349‑7006.2007.00607.x17888036
     [Google Scholar]
  3. GazdarA.F. Activating and resistance mutations of EGFR in non-small-cell lung cancer: Role in clinical response to EGFR tyrosine kinase inhibitors.Oncogene2009281243110.1038/onc.2009.198
     [Google Scholar]
  4. SharmaS.V. BellD.W. SettlemanJ. HaberD.A. Epidermal growth factor receptor mutations in lung cancer.Nat. Rev. Cancer20077316918110.1038/nrc208817318210
     [Google Scholar]
  5. YuanS. YuS.L. ChenH.Y. HsuY.C. SuK.Y. ChenH.W. ChenC.Y. YuC.J. ShihJ.Y. ChangY.L. ChengC.L. HsuC.P. HsiaJ.Y. LinC.Y. WuG. LiuC.H. WangC.D. YangK.C. ChenY.W. LaiY.L. HsuC.C. LinT.C. YangT.Y. ChenK.C. HsuK.H. ChenJ.J.W. ChangG.C. LiK.C. YangP.C. Clustered genomic alterations in chromosome 7p dictate outcomes and targeted treatment responses of lung adenocarcinoma with EGFR-activating mutations.J. Clin. Oncol.201129253435344210.1200/JCO.2011.35.397921810691
     [Google Scholar]
  6. ReitaD. PabstL. PencreachE. GuérinE. DanoL. RimelenV. VoegeliA.C. VallatL. MascauxC. Beau-FallerM. Molecular mechanism of EGFR-TKI Resistance in EGFR-mutated non-small cell lung cancer: Application to biological diagnostic and monitoring.Cancers20211319492610.3390/cancers1319492634638411
     [Google Scholar]
  7. YangZ. YangN. OuQ. XiangY. JiangT. WuX. BaoH. TongX. WangX. ShaoY.W. LiuY. WangY. ZhouC. Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non–small cell lung cancer patients.Clin. Cancer Res.201824133097310710.1158/1078‑0432.CCR‑17‑231029506987
     [Google Scholar]
  8. NiederstM.J. HuH. MulveyH.E. LockermanE.L. GarciaA.R. PiotrowskaZ. SequistL.V. EngelmanJ.A. The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies.Clin. Cancer Res.201521173924393310.1158/1078‑0432.CCR‑15‑056025964297
     [Google Scholar]
  9. LeonettiA. SharmaS. MinariR. PeregoP. GiovannettiE. TiseoM. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer.Br. J. Cancer2019121972573710.1038/s41416‑019‑0573‑831564718
     [Google Scholar]
  10. KilroyM.K. ParkS. FerozW. PatelH. MishraR. AlanaziS. GarrettJ.T. HER3 Alterations in cancer and potential clinical implications.Cancers20221424617410.3390/cancers1424617436551663
     [Google Scholar]
  11. GrabeT. LategahnJ. RauhD. C797S resistance: The Undruggable EGFR mutation in non-small cell lung cancer?ACS Med. Chem. Lett.20189877978210.1021/acsmedchemlett.8b0031430128066
     [Google Scholar]
  12. MokT.S. WuY.L. AhnM.J. GarassinoM.C. KimH.R. RamalingamS.S. ShepherdF.A. HeY. AkamatsuH. TheelenW.S.M.E. LeeC.K. SebastianM. TempletonA. MannH. MarottiM. GhiorghiuS. PapadimitrakopoulouV.A. InvestigatorsA. Osimertinib or Platinum–Pemetrexed in EGFR T790M–positive lung cancer.N. Engl. J. Med.2017376762964010.1056/NEJMoa161267427959700
     [Google Scholar]
  13. MuY. HaoX. XingP. HuX. WangY. LiT. ZhangJ. XuZ. LiJ. Acquired resistance to osimertinib in patients with non-small-cell lung cancer: Mechanisms and clinical outcomes.J. Cancer Res. Clin. Oncol.202014692427243310.1007/s00432‑020‑03239‑132385709
     [Google Scholar]
  14. JohnsonM. GarassinoM.C. MokT. MitsudomiT. Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies.Lung Cancer2022170415110.1016/j.lungcan.2022.05.01135714425
     [Google Scholar]
  15. RamalingamS.S. VansteenkisteJ. PlanchardD. ChoB.C. GrayJ.E. OheY. ZhouC. ReungwetwattanaT. ChengY. ChewaskulyongB. ShahR. CoboM. LeeK.H. CheemaP. TiseoM. JohnT. LinM.C. ImamuraF. KurataT. ToddA. HodgeR. SaggeseM. RukazenkovY. SoriaJ.C. InvestigatorsF. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC.N. Engl. J. Med.20203821415010.1056/NEJMoa191366231751012
     [Google Scholar]
  16. TanC.S. KumarakulasingheN.B. HuangY.Q. AngY.L.E. ChooJ.R.E. GohB.C. SooR.A. Third generation EGFR TKIs: Current data and future directions.Mol. Cancer20181712910.1186/s12943‑018‑0778‑029455654
     [Google Scholar]
  17. JänneP.A. OuS.H.I. KimD.W. OxnardG.R. MartinsR. KrisM.G. DunphyF. NishioM. O’ConnellJ. PaweletzC. TaylorI. ZhangH. GoldbergZ. MokT. Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: A multicentre, open-label, phase 2 trial.Lancet Oncol.201415131433144110.1016/S1470‑2045(14)70461‑925456362
     [Google Scholar]
  18. HarrisonP.T. VyseS. HuangP.H. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer.Semin. Cancer Biol.20206116717910.1016/j.semcancer.2019.09.01531562956
     [Google Scholar]
  19. StewartE.L. TanS.Z. LiuG. TsaoM.S. Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations-a review.Transl. Lung Cancer Res.201541678125806347
     [Google Scholar]
  20. KoulourisA. TsagkarisC. CorrieroA.C. MetroG. MountziosG. Resistance to TKIs in EGFR-mutated non-small cell lung cancer: From mechanisms to new therapeutic strategies.Cancers20221414333710.3390/cancers1414333735884398
     [Google Scholar]
  21. OsoegawaA. YamaguchiM. NakamuraT. MorinagaR. TanakaK. KashiwabaraK. MiuraT. SuetsuguT. HaradaT. AsohT. TaguchiK. NabeshimaK. KishimotoJ. SakaiK. NishioK. SugioK. High incidence of C797S mutation in patients with long treatment history of EGFR tyrosine kinase inhibitors including osimertinib.JTO Clinical and Research Reports20212710019110.1016/j.jtocrr.2021.10019134590037
     [Google Scholar]
  22. ByrneD.P. FoulkesD.M. EyersP.A. Pseudokinases: Update on their functions and evaluation as new drug targets.Future Med. Chem.20179224526510.4155/fmc‑2016‑020728097887
     [Google Scholar]
  23. KungJ.E. JuraN. Prospects for pharmacological targeting of pseudokinases.Nat. Rev. Drug Discov.201918750152630850748
     [Google Scholar]
  24. JänneP.A. BaikC. SuW.C. JohnsonM.L. HayashiH. NishioM. KimD.W. KoczywasM. GoldK.A. SteuerC.E. MurakamiH. YangJ.C.H. KimS.W. VigliottiM. ShiR. QiZ. QiuY. ZhaoL. SternbergD. YuC. YuH.A. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor–resistant, EGFR -mutated non–small cell lung cancer.Cancer Discov.2022121748910.1158/2159‑8290.CD‑21‑071534548309
     [Google Scholar]
  25. ScharpenseelH. HanssenA. LogesS. MohmeM. BernreutherC. PeineS. LamszusK. GoyY. PetersenC. WestphalM. GlatzelM. RiethdorfS. PantelK. WikmanH. EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients.Sci. Rep.201991740610.1038/s41598‑019‑43678‑631092882
     [Google Scholar]
  26. InakiK. ShibutaniT. MaedaN. Eppenberger-CastoriS. NicoletS. KanedaY. KoyamaK. QiuY. WakitaK. MurakamiM. Pan-cancer gene expression analysis of tissue microarray using EdgeSeq oncology biomarker panel and a cross-comparison with HER2 and HER3 immunohistochemical analysis.PLoS One2022179e027414010.1371/journal.pone.027414036137139
     [Google Scholar]
  27. LiQ. ZhangR. YanH. ZhaoP. WuL. WangH. LiT. CaoB. Prognostic significance of HER3 in patients with malignant solid tumors.Oncotarget2017840671406715110.18632/oncotarget.1800728978022
     [Google Scholar]
  28. KawanoO. SasakiH. EndoK. SuzukiE. HanedaH. YukiueH. KobayashiY. YanoM. FujiiY. ErbB3 mRNA expression correlated with specific clinicopathologic features of Japanese lung cancers.J. Surg. Res.20081461434810.1016/j.jss.2007.05.03017631905
     [Google Scholar]
  29. SithanandamG. FornwaldL.W. FieldsJ. AndersonL.M. Inactivation of ErbB3 by siRNA promotes apoptosis and attenuates growth and invasiveness of human lung adenocarcinoma cell line A549.Oncogene200524111847185910.1038/sj.onc.120838115688028
     [Google Scholar]
  30. YiE.S. HarclerodeD. GondoM. StephensonM. BrownR.W. YounesM. CagleP.T. High c-erbB-3 protein expression is associated with shorter survival in advanced non-small cell lung carcinomas.Mod. Pathol.19971021421489127320
     [Google Scholar]
  31. HaikalaH.M. JänneP.A. Thirty years of HER3: From basic biology to therapeutic interventions.Clin. Cancer Res.202127133528353910.1158/1078‑0432.CCR‑20‑446533608318
     [Google Scholar]
  32. Gandullo-SánchezL. OcañaA. PandiellaA. HER3 in cancer: From the bench to the bedside.J. Exp. Clin. Cancer Res.202241131010.1186/s13046‑022‑02515‑x36271429
     [Google Scholar]
  33. HaikalaH.M. LopezT. KöhlerJ. EserP.O. XuM. ZengQ. TecenoT.J. NgoK. ZhaoY. IvanovaE.V. BertramA.A. LeeperB.A. ChambersE.S. AdeniA.E. TausL.J. KuraguchiM. KirschmeierP.T. YuC. ShioseY. KamaiY. QiuY. PaweletzC.P. GokhaleP.C. JänneP.A. EGFR Inhibition enhances the cellular uptake and antitumor-activity of the HER3 antibody–drug conjugate HER3–DXd.Cancer Res.202282113014110.1158/0008‑5472.CAN‑21‑242634548332
     [Google Scholar]
  34. YonesakaK. TakegawaN. WatanabeS. HarataniK. KawakamiH. SakaiK. ChibaY. MaedaN. KagariT. HirotaniK. NishioK. NakagawaK. An HER3-targeting antibody–drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC.Oncogene20193891398140910.1038/s41388‑018‑0517‑430302022
     [Google Scholar]
  35. YonesakaK. TanizakiJ. MaenishiO. HarataniK. KawakamiH. TanakaK. HayashiH. SakaiK. ChibaY. TsuyaA. GotoH. OtsukaE. OkidaH. KobayashiM. YoshimotoR. FunabashiM. HashimotoY. HirotaniK. KagariT. NishioK. NakagawaK. HER3 augmentation via blockade of EGFR/AKT signaling enhances anticancer activity of HER3-targeting patritumab deruxtecan in EGFR-mutated non–small cell lung cancer.Clin. Cancer Res.202228239040310.1158/1078‑0432.CCR‑21‑335934921025
     [Google Scholar]
  36. EngelmanJ.A. ZejnullahuK. MitsudomiT. SongY. HylandC. ParkJ.O. LindemanN. GaleC.M. ZhaoX. ChristensenJ. KosakaT. HolmesA.J. RogersA.M. CappuzzoF. MokT. LeeC. JohnsonB.E. CantleyL.C. JänneP.A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.Science200731658271039104310.1126/science.114147817463250
     [Google Scholar]
  37. SchoenfeldA.J. YuH.A. The evolving landscape of resistance to osimertinib.J. Thorac. Oncol.2020151182110.1016/j.jtho.2019.11.00531864549
     [Google Scholar]
  38. LeX. PuriS. NegraoM.V. NilssonM.B. RobichauxJ. BoyleT. HicksJ.K. LovingerK.L. RoartyE. RinsurongkawongW. TangM. SunH. ElaminY. LacerdaL.C. LewisJ. RothJ.A. SwisherS.G. LeeJ.J. WilliamW.N.Jr GlissonB.S. ZhangJ. PapadimitrakopoulouV.A. GrayJ.E. HeymachJ.V. Landscape of EGFR-dependent and -independent resistance mechanisms to osimertinib and continuation therapy beyond progression in EGFR -Mutant NSCLC.Clin. Cancer Res.201824246195620310.1158/1078‑0432.CCR‑18‑154230228210
     [Google Scholar]
  39. OxnardG.R. HuY. MilehamK.F. HusainH. CostaD.B. TracyP. FeeneyN. ShollL.M. DahlbergS.E. RedigA.J. KwiatkowskiD.J. RabinM.S. PaweletzC.P. ThressK.S. JänneP.A. Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M–Positive lung cancer and acquired resistance to osimertinib.JAMA Oncol.20184111527153410.1001/jamaoncol.2018.296930073261
     [Google Scholar]
  40. PiotrowskaZ. IsozakiH. LennerzJ.K. GainorJ.F. LennesI.T. ZhuV.W. MarcouxN. BanwaitM.K. DigumarthyS.R. SuW. YodaS. RileyA.K. NangiaV. LinJ.J. NagyR.J. LanmanR.B. Dias-SantagataD. Mino-KenudsonM. IafrateA.J. HeistR.S. ShawA.T. EvansE.K. CliffordC. OuS.H.I. WolfB. HataA.N. SequistL.V. Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion.Cancer Discov.20188121529153910.1158/2159‑8290.CD‑18‑102230257958
     [Google Scholar]
  41. KrausM.H. IssingW. MikiT. PopescuN.C. AaronsonS.A. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.Proc. Natl. Acad. Sci. USA198986239193919710.1073/pnas.86.23.91932687875
     [Google Scholar]
  42. JuraN. ShanY. CaoX. ShawD.E. KuriyanJ. Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3.Proc. Natl. Acad. Sci. USA200910651216082161310.1073/pnas.091210110620007378
     [Google Scholar]
  43. BerginskiM.E. MoretN. LiuC. GoldfarbD. SorgerP.K. GomezS.M. The Dark Kinase Knowledgebase: An online compendium of knowledge and experimental results of understudied kinases.Nucleic Acids Res.202149D1D529D53510.1093/nar/gkaa85333079988
     [Google Scholar]
  44. ManningG. WhyteD.B. MartinezR. HunterT. SudarsanamS. The protein kinase complement of the human genome.Science200229856001912193410.1126/science.107576212471243
     [Google Scholar]
  45. MishraR. PatelH. AlanaziS. YuanL. GarrettJ.T. HER3 signaling and targeted therapy in cancer.Oncol. Rev.201812135510.4081/oncol.2018.35530057690
     [Google Scholar]
  46. CampbellM.R. AminD. MoasserM.M. HER3 comes of age: New insights into its functions and role in signaling, tumor biology, and cancer therapy.Clin. Cancer Res.20101651373138310.1158/1078‑0432.CCR‑09‑121820179223
     [Google Scholar]
  47. LiC. BrandT.M. IidaM. HuangS. ArmstrongE.A. van der KogelA. WheelerD.L. Human epidermal growth factor receptor 3 (HER3) blockade with U3-1287/AMG888 enhances the efficacy of radiation therapy in lung and head and neck carcinoma.Discov. Med.20131687799223998444
     [Google Scholar]
  48. MirschbergerC. SchillerC.B. SchrämlM. DimoudisN. FriessT. GerdesC.A. ReiffU. LifkeV. HoelzlwimmerG. KolmI. HopfnerK.P. NiederfellnerG. BossenmaierB. RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation.Cancer Res.201373165183519410.1158/0008‑5472.CAN‑13‑009923780344
     [Google Scholar]
  49. KimH.S. HanJ.Y. ShinD.H. LimK.Y. LeeG.K. KimJ.Y. JacobW. CeppiM. WeisserM. JamesI. EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion.Lung Cancer2018124717510.1016/j.lungcan.2018.07.02630268483
     [Google Scholar]
  50. SequistL.V. GrayJ.E. HarbW.A. Lopez-ChavezA. DoebeleR.C. ModianoM.R. JackmanD.M. BaggstromM.Q. AtmacaA. FelipE. ProvencioM. CoboM. AdiwijayaB. KuestersG. KamounW.S. AndreasK. PipasJ.M. SantillanaS. ChoB.C. ParkK. ShepherdF.A. Randomized Phase II Trial of seribantumab in combination with erlotinib in patients with EGFR wild- type non-small cell lung cancer.Oncologist20192481095110210.1634/theoncologist.2018‑069530975923
     [Google Scholar]
  51. MeulendijksD. JacobW. Martinez-GarciaM. TausA. LolkemaM.P. VoestE.E. LangenbergM.H.G. Fleitas KanonnikoffT. CervantesA. De JongeM.J. SleijferS. SoerensenM.M. ThomasM. CeppiM. Meneses-LorenteG. JamesI. AdessiC. MichielinF. AbirajK. BossenmaierB. SchellensJ.H.M. WeisserM. LassenU.N. First-in-Human Phase I Study of Lumretuzumab, a glycoengineered humanized Anti-HER3 monoclonal antibody, in patients with metastatic or advanced HER3-positive solid tumors.Clin. Cancer Res.201622487788510.1158/1078‑0432.CCR‑15‑168326463709
     [Google Scholar]
  52. MeulendijksD. JacobW. VoestE.E. Mau-SorensenM. Martinez-GarciaM. TausA. FleitasT. CervantesA. LolkemaM.P. LangenbergM.H.G. De JongeM.J. SleijferS. HanJ.Y. CallesA. FelipE. KimS.W. SchellensJ.H.M. WilsonS. ThomasM. CeppiM. Meneses-LorenteG. JamesI. Vega-HarringS. DuaR. NguyenM. SteinerL. AdessiC. MichielinF. BossenmaierB. WeisserM. LassenU.N. Phase Ib study of lumretuzumab plus cetuximab or erlotinib in solid tumor patients and evaluation of HER3 and heregulin as potential biomarkers of clinical activity.Clin. Cancer Res.201723185406541510.1158/1078‑0432.CCR‑17‑081228600476
     [Google Scholar]
  53. YardenY. SliwkowskiM.X. Untangling the ErbB signalling network.Nat. Rev. Mol. Cell Biol.20012212713710.1038/3505207311252954
     [Google Scholar]
  54. BaselgaJ. SwainS.M. Novel anticancer targets: Revisiting ERBB2 and discovering ERBB3.Nat. Rev. Cancer20099746347510.1038/nrc265619536107
     [Google Scholar]
  55. SequistL.V. JanneP.A. HuberR.M. GrayJ.E. FelipE. PerolM. HirschF.R. TanD.S.W. KuestersG. ZalutskayaA. SantillanaS. PipasJ.M. ShepherdF.A. SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).J. Clin. Oncol.20193715_suppl9036903610.1200/JCO.2019.37.15_suppl.9036
     [Google Scholar]
  56. YonesakaK. HirotaniK. KawakamiH. TakedaM. KanedaH. SakaiK. OkamotoI. NishioK. JänneP.A. NakagawaK. Anti-HER3 monoclonal antibody patritumab sensitizes refractory non-small cell lung cancer to the epidermal growth factor receptor inhibitor erlotinib.Oncogene201635787888610.1038/onc.2015.14225961915
     [Google Scholar]
  57. TrederM. OgbagabrielS. MoorR. Schulze-HorselU. HettmannT. RotheM. RadinskyR. FreemanD. 309 POSTER Fully human anti-HER3 mAb U3-1287 (AMG 888) demonstrates unique in vitro and in vivo activities versus other HER family inhibitors in NSCLC models.Eur. J. Cancer Suppl.20086129910.1016/S1359‑6349(08)72243‑2
     [Google Scholar]
  58. SankyoD. Daiichi Sankyo provides update on her3-lung study of patritumab in non-small cell lung cancer.Available from: https://www.prnewswire.com/news-releases/daiichi-sankyo-provides-update-on-her3-lung-study-of-patritumab-in-non-small-cell-lung-cancer-nsclc-300276710.html
  59. DolginE. HER3-addicted tumors: How biotechs are closing in.Nat. Biotechnol.20224081157115910.1038/s41587‑022‑01425‑935945436
     [Google Scholar]
  60. CampbellM.R. Ruiz-SaenzA. PetersonE. AgnewC. AyazP. GarfinkleS. LittlefieldP. SteriV. OeffingerJ. SampangM. ShanY. ShawD.E. JuraN. MoasserM.M. Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers.Cell Rep.202238511029110.1016/j.celrep.2021.11029135108525
     [Google Scholar]
  61. De NardisC. HendriksL.J.A. PoirierE. ArvinteT. GrosP. BakkerA.B.H. de KruifJ. A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1.J. Biol. Chem.201729235147061471710.1074/jbc.M117.79349728655766
     [Google Scholar]
  62. de Vries SchultinkA.H.M. BolK. DoornbosR.P. MuratA. WassermanE. DorloT.P.C. SchellensJ.H.M. BeijnenJ.H. HuitemaA.D.R. Population pharmacokinetics of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, in patients with solid tumors.Clin. Pharmacokinet.202059787588410.1007/s40262‑020‑00858‑232006223
     [Google Scholar]
  63. MCLA-128 fights NRG1 fusion-positive cancersCancer Discov.2019912163610.1158/2159‑8290.CD‑NB2019‑12831685488
     [Google Scholar]
  64. HashimotoY. KoyamaK. KamaiY. HirotaniK. OgitaniY. ZembutsuA. AbeM. KanedaY. MaedaN. ShioseY. IguchiT. IshizakaT. KaribeT. HayakawaI. MoritaK. NakadaT. NomuraT. WakitaK. KagariT. AbeY. MurakamiM. UenoS. AgatsumaT. A novel HER3-targeting antibody–drug conjugate, U3-1402, exhibits potent therapeutic efficacy through the delivery of cytotoxic payload by efficient internalization.Clin. Cancer Res.201925237151716110.1158/1078‑0432.CCR‑19‑174531471314
     [Google Scholar]
  65. OgitaniY. AbeY. IguchiT. YamaguchiJ. TerauchiT. KitamuraM. GotoK. GotoM. OitateM. YukinagaH. YabeY. NakadaT. MasudaT. MoritaK. AgatsumaT. Wide application of a novel topoisomerase I inhibitor-based drug conjugation technology.Bioorg. Med. Chem. Lett.201626205069507210.1016/j.bmcl.2016.08.08227599744
     [Google Scholar]
  66. NakadaT. MasudaT. NaitoH. YoshidaM. AshidaS. MoritaK. MiyazakiH. KasuyaY. OgitaniY. YamaguchiJ. AbeY. HondaT. Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads.Bioorg. Med. Chem. Lett.20162661542154510.1016/j.bmcl.2016.02.02026898815
     [Google Scholar]
  67. OgitaniY. AidaT. HagiharaK. YamaguchiJ. IshiiC. HaradaN. SomaM. OkamotoH. OitateM. ArakawaS. HiraiT. AtsumiR. NakadaT. HayakawaI. AbeY. AgatsumaT. DS-8201a, A novel HER2-Targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1.Clin. Cancer Res.201622205097510810.1158/1078‑0432.CCR‑15‑282227026201
     [Google Scholar]
  68. OgitaniY. HagiharaK. OitateM. NaitoH. AgatsumaT. Bystander killing effect of DS -8201a, a novel anti-human epidermal growth factor receptor 2 antibody–drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity.Cancer Sci.201610771039104610.1111/cas.1296627166974
     [Google Scholar]
  69. DoiT. ShitaraK. NaitoY. ShimomuraA. FujiwaraY. YonemoriK. ShimizuC. ShimoiT. KubokiY. MatsubaraN. KitanoA. JikohT. LeeC. FujisakiY. OgitaniY. YverA. TamuraK. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody–drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study.Lancet Oncol.201718111512152210.1016/S1470‑2045(17)30604‑629037983
     [Google Scholar]
  70. KawakamiH. OkamotoI. YonesakaK. OkamotoK. ShibataK. ShinkaiY. SakamotoH. KitanoM. TamuraT. NishioK. NakagawaK. The anti-HER3 antibody patritumab abrogates cetuximab resistance mediated by heregulin in colorectal cancer cells.Oncotarget2014523118471185610.18632/oncotarget.266325474137
     [Google Scholar]
  71. LoRussoP. JänneP.A. OliveiraM. RizviN. MalburgL. KeedyV. YeeL. CopigneauxC. HettmannT. WuC.Y. AngA. HalimA.B. BeckmanR.A. BeaupreD. BerlinJ. Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors.Clin. Cancer Res.201319113078308710.1158/1078‑0432.CCR‑12‑305123591447
     [Google Scholar]
  72. WakuiH. YamamotoN. NakamichiS. TamuraY. NokiharaH. YamadaY. TamuraT. Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors.Cancer Chemother. Pharmacol.201473351151610.1007/s00280‑014‑2375‑224442032
     [Google Scholar]
  73. HarataniK. YonesakaK. TakamuraS. MaenishiO. KatoR. TakegawaN. KawakamiH. TanakaK. HayashiH. TakedaM. MaedaN. KagariT. HirotaniK. TsurutaniJ. NishioK. DoiK. MiyazawaM. NakagawaK. U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation.J. Clin. Invest.2019130137438810.1172/JCI12659831661465
     [Google Scholar]
  74. SchoeberlB. PaceE.A. FitzgeraldJ.B. HarmsB.D. XuL. NieL. LinggiB. KalraA. ParagasV. BukhalidR. GrantcharovaV. KohliN. WestK.A. LeszczynieckaM. FeldhausM.J. KudlaA.J. NielsenU.B. Therapeutically targeting ErbB3: A key node in ligand-induced activation of the ErbB receptor-PI3K axis.Sci. Signal.2009277ra3110.1126/scisignal.200035219567914
     [Google Scholar]
  75. SteuerC.E. HayashiH. SuW.C. NishioM. JohnsonM.L. KimD.W. KoczywasM. FelipE. GoldK.A. MurakamiH. BaikC.S. KimS.W. SmitE.F. GigantoneM. KimB. FanP.D. QiZ. WuE.Y. SternbergD.W. JanneP.A. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in advanced/metastatic non-small cell lung cancer (NSCLC) without EGFR-activating mutations.J. Clin. Oncol.20224016_supplSuppl. 169017901710.1200/JCO.2022.40.16_suppl.9017
     [Google Scholar]
  76. YuH.A. YangJ.C. HayashiH. GotoY. FelipE. ReckM. VigliottiM. DongQ. CanteroF. FanP.D. KanaiM. SternbergD.W. JänneP.A. HERTHENA-Lung01: A phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC.Future Oncol.202319191319132910.2217/fon‑2022‑125037212796
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673269305231115102542
Loading
The Therapeutic Significance of HER3 in Non-small Cell Lung Cancer (NSCLC): A Review Study
Curr. Med. Chem. 32, 434 (2025); https://doi.org/10.2174/0109298673269305231115102542
/content/journals/cmc/10.2174/0109298673269305231115102542
/content/journals/cmc/10.2174/0109298673269305231115102542
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): clinical trials; HER3; monoclonal antibody; non-small cell lung cancer; therapeutics; tyrosine kinase inhibitor

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test