Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Medicinal Chemistry
  4. Fast Track Articles
  5. Fast Track Article
image of HER3-targeting Antibody-drug Conjugates Therapy for Solid Tumors: Recent Advances and Future Potentials

Abstract

In most advanced cancers, standard medical treatments are generally employed. With the emergence of Antibody-Drug Conjugates (ADCs), more optimal therapeutic methods have become available for treating tumors. ADC is composed of a monoclonal antibody that targets a specific antigen and a cytotoxic payload, which conjugates the synthetic linkers. Therefore, ADC combines the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity. Besides, the epidermal growth factor receptor (EGFR) family, expressing differently between tumors and normal tissues, is one of the most frequently targeted antigens for ADC therapy, which mainly encompasses EGFR1/ErbB1, human epidermal growth factor receptor 2/ epidermal growth factor receptor 2 (HER2/ErbB2), HER3/ErbB3, and HER4/ErbB4. In contrast to other targets, HER3 stands out as a promising one, closely associated with the pathogenesis of treatment resistance in several cancers. Moreover, solid tumors, which are more prevalent than hematological malignancies, present a vast field of opportunities for the development of HER3-targeting ADCs. However, research on HER3-targeting ADCs treating solid tumors remains insufficient. Therefore, it is imperative for researchers to gather more clinical trial data and continue to elucidate the efficacy and safety of HER3-ADCs in solid tumors. This review summarizes recent advances and future potentials, aiming to provide insights into targeted therapy. We hope that this review will provide useful information to physicians in the field.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673358929250213093803
2025-02-24
2025-04-01

  • From This Site

    /content/journals/cmc/10.2174/0109298673358929250213093803
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Siegel R.L. Miller K.D. Wagle N.S. Jemal A. Cancer statistics, 2023. CA Cancer J. Clin. 2023 73 1 17 48 10.3322/caac.21763 36633525
    [Google Scholar]
  2. Giaquinto A.N. Sung H. Miller K.D. Kramer J.L. Newman L.A. Minihan A. Jemal A. Siegel R.L. Breast cancer statistics. CA Cancer J. Clin. 2022 72 6 524 541 10.3322/caac.21754 36190501
    [Google Scholar]
  3. Lindley C. McCune J.S. Thomason T.E. Lauder D. Sauls A. Adkins S. Sawyer W.T. Perception of chemotherapy side effects cancer versus noncancer patients. Cancer Pract. 1999 7 2 59 65 10.1046/j.1523‑5394.1999.07205.x 10352062
    [Google Scholar]
  4. Geyer C.E. Forster J. Lindquist D. Chan S. Romieu C.G. Pienkowski T. Jagiello-Gruszfeld A. Crown J. Chan A. Kaufman B. Skarlos D. Campone M. Davidson N. Berger M. Oliva C. Rubin S.D. Stein S. Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 2006 355 26 2733 2743 10.1056/NEJMoa064320 17192538
    [Google Scholar]
  5. Fu Z. Li S. Han S. Shi C. Zhang Y. Antibody drug conjugate: The “biological missile” for targeted cancer therapy. Signal Transduct. Target. Ther. 2022 7 1 93 10.1038/s41392‑022‑00947‑7 35318309
    [Google Scholar]
  6. Desai A. Abdayem P. Adjei A.A. Planchard D. Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. Lung Cancer 2022 163 96 106 10.1016/j.lungcan.2021.12.002 34942494
    [Google Scholar]
  7. Fuentes-Antrás J. Genta S. Vijenthira A. Siu L.L. Antibody–drug conjugates: In search of partners of choice. Trends Cancer 2023 9 4 339 354 10.1016/j.trecan.2023.01.003 36746689
    [Google Scholar]
  8. Guo H. Zhang J. Qin C. Yan H. Liu T. Hu H. Tang S. Tang S. Zhou H. Biomarker-targeted therapies in non–small cell lung cancer: Current status and perspectives. Cells 2022 11 20 3200 10.3390/cells11203200 36291069
    [Google Scholar]
  9. Smith S.M. Wachter K. Burris H.A. III Schilsky R.L. George D.J. Peterson D.E. Johnson M.L. Markham M.J. Mileham K.F. Beg M.S. Bendell J.C. Dreicer R. Keedy V.L. Kimple R.J. Knoll M.A. LoConte N. MacKay H. Meisel J.L. Moynihan T.J. Mulrooney D.A. Mulvey T.M. Odenike O. Pennell N.A. Reeder-Hayes K. Smith C. Sullivan R.J. Uzzo R. Clinical cancer advances 2021: ASCO’s report on progress against cancer. J. Clin. Oncol. 2021 39 10 1165 1184 10.1200/JCO.20.03420 33527845
    [Google Scholar]
  10. Nicolò E. Repetto M. Boscolo Bielo L. Tarantino P. Curigliano G. E N Antibody-Drug conjugates in breast cancer: What is beyond HER2? Cancer J. 2022 28 6 436 445 10.1097/PPO.0000000000000629 36383906
    [Google Scholar]
  11. Nagayama A. Ellisen L.W. Chabner B. Bardia A. antibody–drug conjugates for the treatment of solid tumors: Clinical experience and latest developments. Target. Oncol. 2017 12 6 719 739 10.1007/s11523‑017‑0535‑0 29116596
    [Google Scholar]
  12. Beck A. Goetsch L. Dumontet C. Corvaïa N. Strategies and challenges for the next generation of antibody–drug conjugates. Nat. Rev. Drug Discov. 2017 16 5 315 337 10.1038/nrd.2016.268 28303026
    [Google Scholar]
  13. Drago J.Z. Modi S. Chandarlapaty S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nat. Rev. Clin. Oncol. 2021 18 6 327 344 10.1038/s41571‑021‑00470‑8 33558752
    [Google Scholar]
  14. Lu G. Nishio N. van den Berg N.S. Martin B.A. Fakurnejad S. van Keulen S. Colevas A.D. Thurber G.M. Rosenthal E.L. Co-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates. Nat. Commun. 2020 11 1 5667 10.1038/s41467‑020‑19498‑y 33168818
    [Google Scholar]
  15. Ogitani Y. Hagihara K. Oitate M. Naito H. Agatsuma T. 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. 2016 107 7 1039 1046 10.1111/cas.12966 27166974
    [Google Scholar]
  16. Verma S. Miles D. Gianni L. Krop I.E. Welslau M. Baselga J. Pegram M. Oh D.Y. Diéras V. Guardino E. Fang L. Lu M.W. Olsen S. Blackwell K. EMILIA Study Group Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 2012 367 19 1783 1791 10.1056/NEJMoa1209124 23020162
    [Google Scholar]
  17. Diéras V. Miles D. Verma S. Pegram M. Welslau M. Baselga J. Krop I.E. Blackwell K. Hoersch S. Xu J. Green M. Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): A descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 18 6 732 742 10.1016/S1470‑2045(17)30312‑1 28526536
    [Google Scholar]
  18. Li Q. Zhang R. Yan H. Zhao P. Wu L. Wang H. Li T. Cao B. Prognostic significance of HER3 in patients with malignant solid tumors. Oncotarget 2017 8 40 67140 67151 10.18632/oncotarget.18007 28978022
    [Google Scholar]
  19. Miano C. Morselli A. Pontis F. Bongiovanni C. Sacchi F. Da Pra S. Romaniello D. Tassinari R. Sgarzi M. Pantano E. Ventura C. Lauriola M. D’Uva G. NRG1/ERBB3/ERBB2 axis triggers anchorage-independent growth of basal-like/triple-negative breast cancer cells. Cancers 2022 14 7 1603 10.3390/cancers14071603 35406375
    [Google Scholar]
  20. Wu X. Chen Y. Li G. Xia L. Gu R. Wen X. Ming X. Chen H. Her3 is associated with poor survival of gastric adenocarcinoma: Her3 promotes proliferation, survival and migration of human gastric cancer mediated by PI3K/AKT signaling pathway. Med. Oncol. 2014 31 4 903 10.1007/s12032‑014‑0903‑x 24623015
    [Google Scholar]
  21. Scharpenseel H. Hanssen A. Loges S. Mohme M. Bernreuther C. Peine S. Lamszus K. Goy Y. Petersen C. Westphal M. Glatzel M. Riethdorf S. Pantel K. Wikman H. EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients. Sci. Rep. 2019 9 1 7406 10.1038/s41598‑019‑43678‑6 31092882
    [Google Scholar]
  22. Boch T. Köhler J. Janning M. Loges S. Targeting the EGF receptor family in non-small cell lung cancer—increased complexity and future perspectives. Cancer Biol. Med. 2022 19 11 1543 1564 10.20892/j.issn.2095‑3941.2022.0540 36476337
    [Google Scholar]
  23. Engelman J.A. Zejnullahu K. Mitsudomi T. Song Y. Hyland C. Park J.O. Lindeman N. Gale C.M. Zhao X. Christensen J. Kosaka T. Holmes A.J. Rogers A.M. Cappuzzo F. Mok T. Lee C. Johnson B.E. Cantley L.C. Jänne P.A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007 316 5827 1039 1043 10.1126/science.1141478 17463250
    [Google Scholar]
  24. Yonesaka K. Tanizaki J. Maenishi O. Haratani K. Kawakami H. Tanaka K. Hayashi H. Sakai K. Chiba Y. Tsuya A. Goto H. Otsuka E. Okida H. Kobayashi M. Yoshimoto R. Funabashi M. Hashimoto Y. Hirotani K. Kagari T. Nishio K. Nakagawa K. 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. 2022 28 2 390 403 10.1158/1078‑0432.CCR‑21‑3359 34921025
    [Google Scholar]
  25. Maennling A.E. Tur M.K. Niebert M. Klockenbring T. Zeppernick F. Gattenlöhner S. Meinhold-Heerlein I. Hussain A.F. Molecular targeting therapy against EGFR family in breast cancer: Progress and future potentials. Cancers 2019 11 12 1826 10.3390/cancers11121826 31756933
    [Google Scholar]
  26. Hutcheson I.R. Goddard L. Barrow D. McClelland R.A. Francies H.E. Knowlden J.M. Nicholson R.I. Gee J.M.W. Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin β1. Breast Cancer Res. 2011 13 2 R29 10.1186/bcr2848 21396094
    [Google Scholar]
  27. Mishra R. Patel H. Alanazi S. Yuan L. Garrett J.T. HER3 signaling and targeted therapy in cancer. Oncol. Rev. 2018 12 1 355 10.4081/oncol.2018.355 30057690
    [Google Scholar]
  28. Kiavue N. Cabel L. Melaabi S. Bataillon G. Callens C. Lerebours F. Pierga J.Y. Bidard F.C. ERBB3 mutations in cancer: Biological aspects, prevalence and therapeutics. Oncogene 2020 39 3 487 502 10.1038/s41388‑019‑1001‑5 31519989
    [Google Scholar]
  29. Zeng H. Wang W. Zhang L. Lin Z. HER3-targeted therapy: The mechanism of drug resistance and the development of anticancer drugs. Cancer Drug Resist. 2024 7 14 10.20517/cdr.2024.11 38835349
    [Google Scholar]
  30. Jura N. Shan Y. Cao X. Shaw D.E. Kuriyan J. Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3. Proc. Natl. Acad. Sci. USA 2009 106 51 21608 21613 10.1073/pnas.0912101106 20007378
    [Google Scholar]
  31. Shi F. Telesco S.E. Liu Y. Radhakrishnan R. Lemmon M.A. ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc. Natl. Acad. Sci. USA 2010 107 17 7692 7697 10.1073/pnas.1002753107 20351256
    [Google Scholar]
  32. Berger M.B. Mendrola J.M. Lemmon M.A. ErbB3/HER3 does not homodimerize upon neuregulin binding at the cell surface. FEBS Lett. 2004 569 1-3 332 336 10.1016/j.febslet.2004.06.014 15225657
    [Google Scholar]
  33. Kunii K. Davis L. Gorenstein J. Hatch H. Yashiro M. Di Bacco A. Elbi C. Lutterbach B. FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008 68 7 2340 2348 10.1158/0008‑5472.CAN‑07‑5229 18381441
    [Google Scholar]
  34. Haikala H.M. Jänne P.A. Thirty years of HER3: From basic biology to therapeutic interventions. Clin. Cancer Res. 2021 27 13 3528 3539 10.1158/1078‑0432.CCR‑20‑4465 33608318
    [Google Scholar]
  35. Montero J.C. Rodríguez-Barrueco R. Ocaña A. Díaz-Rodríguez E. Esparís-Ogando A. Pandiella A. Neuregulins and cancer. Clin. Cancer Res. 2008 14 11 3237 3241 10.1158/1078‑0432.CCR‑07‑5133 18519747
    [Google Scholar]
  36. Sheng Q. Liu J. The therapeutic potential of targeting the EGFR family in epithelial ovarian cancer. Br. J. Cancer 2011 104 8 1241 1245 10.1038/bjc.2011.62 21364581
    [Google Scholar]
  37. Junttila TT Akita RW Parsons K Phillips G.D. Friedman L.S Sampath D. Sliwkowski M.X. Ligand-independent HER2/HER3/PI3K complex is disrupted by Trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer cell 2009 15 429 440
    [Google Scholar]
  38. Jänne P.A. Baik C. Su W.C. Johnson M.L. Hayashi H. Nishio M. Kim D.W. Koczywas M. Gold K.A. Steuer C.E. Murakami H. Yang J.C.H. Kim S.W. Vigliotti M. Shi R. Qi Z. Qiu Y. Zhao L. Sternberg D. Yu C. Yu H.A. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor–resistant, EGFR -mutated non–small cell lung cancer. Cancer Discov. 2022 12 1 74 89 10.1158/2159‑8290.CD‑21‑0715 34548309
    [Google Scholar]
  39. Pascual T. Oliveira M. Ciruelos E. Bellet Ezquerra M. Saura C. Gavilá J. Pernas S. Muñoz M. Vidal M.J. Margelí Vila M. Cejalvo J.M. González-Farré B. Espinosa-Bravo M. Cruz J. Salvador-Bofill F.J. Guerra J.A. Luna Barrera A.M. Arumi de Dios M. Esker S. Fan P.D. Martínez-Sáez O. Villacampa G. Paré L. Ferrero-Cafiero J.M. Villagrasa P. Prat A. SOLTI-1805 TOT-HER3 study concept: A window-of-opportunity trial of Patritumab Deruxtecan, a HER3 directed antibody drug conjugate, in patients with early breast cancer. Front. Oncol. 2021 11 638482 10.3389/fonc.2021.638482 33968735
    [Google Scholar]
  40. Hashimoto Y. Koyama K. Kamai Y. Hirotani K. Ogitani Y. Zembutsu A. Abe M. Kaneda Y. Maeda N. Shiose Y. Iguchi T. Ishizaka T. Karibe T. Hayakawa I. Morita K. Nakada T. Nomura T. Wakita K. Kagari T. Abe Y. Murakami M. Ueno S. Agatsuma T. 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. 2019 25 23 7151 7161 10.1158/1078‑0432.CCR‑19‑1745 31471314
    [Google Scholar]
  41. Koganemaru S. Kuboki Y. Koga Y. Kojima T. Yamauchi M. Maeda N. Kagari T. Hirotani K. Yasunaga M. Matsumura Y. Doi T. U3-1402, a novel HER3-targeting antibody–drug conjugate, for the treatment of colorectal cancer. Mol. Cancer Ther. 2019 18 11 2043 2050 10.1158/1535‑7163.MCT‑19‑0452 31395690
    [Google Scholar]
  42. Yonesaka K. Takegawa N. Watanabe S. Haratani K. Kawakami H. Sakai K. Chiba Y. Maeda N. Kagari T. Hirotani K. Nishio K. Nakagawa K. An HER3-targeting antibody–drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC. Oncogene 2019 38 9 1398 1409 10.1038/s41388‑018‑0517‑4 30302022
    [Google Scholar]
  43. Hedrich W.D. Fandy T.E. Ashour H.M. Wang H. Hassan H.E. Antibody–drug conjugates: Pharmacokinetic/pharmacodynamic modeling, preclinical characterization, clinical studies, and lessons learned. Clin. Pharmacokinet. 2018 57 6 687 703 10.1007/s40262‑017‑0619‑0 29188435
    [Google Scholar]
  44. Nakada T. Sugihara K. Jikoh T. Abe Y. Agatsuma T. The latest research and development into the antibody–drug conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 cancer therapy. Chem. Pharm. Bull. (Tokyo) 2019 67 3 173 185 10.1248/cpb.c18‑00744 30827997
    [Google Scholar]
  45. Ogitani Y. Aida T. Hagihara K. Yamaguchi J. Ishii C. Harada N. Soma M. Okamoto H. Oitate M. Arakawa S. Hirai T. Atsumi R. Nakada T. Hayakawa I. Abe Y. Agatsuma T. 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. 2016 22 20 5097 5108 10.1158/1078‑0432.CCR‑15‑2822 27026201
    [Google Scholar]
  46. Galluzzi L. Buqué A. Kepp O. Zitvogel L. Kroemer G. Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell 2015 28 6 690 714 10.1016/j.ccell.2015.10.012 26678337
    [Google Scholar]
  47. Koyama K. Ishikawa H. Abe M. Shiose Y. Ueno S. Qiu Y. Nakamaru K. Murakami M. Patritumab deruxtecan (HER3-DXd), a novel HER3 directed antibody drug conjugate, exhibits in vitro activity against breast cancer cells expressing HER3 mutations with and without HER2 overexpression. PLoS One 2022 17 5 e0267027 10.1371/journal.pone.0267027 35503762
    [Google Scholar]
  48. Pauken K.E. Wherry E.J. Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 2015 36 4 265 276 10.1016/j.it.2015.02.008 25797516
    [Google Scholar]
  49. Haratani K. Yonesaka K. Takamura S. Maenishi O. Kato R. Takegawa N. Kawakami H. Tanaka K. Hayashi H. Takeda M. Maeda N. Kagari T. Hirotani K. Tsurutani J. Nishio K. Doi K. Miyazawa M. Nakagawa K. U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation. J. Clin. Invest. 2019 130 1 374 388 10.1172/JCI126598 31661465
    [Google Scholar]
  50. Krop I.E. Masuda N. Mukohara T. Takahashi S. Nakayama T. Inoue K. Iwata H. Yamamoto Y. Alvarez R.H. Toyama T. Takahashi M. Osaki A. Saji S. Sagara Y. O’Shaughnessy J. Ohwada S. Koyama K. Inoue T. Li L. Patel P. Mostillo J. Tanaka Y. Sternberg D.W. Sellami D. Yonemori K. Patritumab Deruxtecan (HER3-DXd), a human epidermal growth factor receptor 3–directed antibody-drug conjugate, in patients with previously treated human epidermal growth factor receptor 3–expressing metastatic breast cancer: A multicenter, phase I/II Trial. J. Clin. Oncol. 2023 41 36 5550 5560 10.1200/JCO.23.00882 37801674
    [Google Scholar]
  51. Yonemori K. Masuda N. Takahashi S. Kogawa T. Nakayama T. Yamamoto Y. Takahashi M. Toyama T. Saeki T. Iwata H. Single agent activity of U3-1402, a HER3-targeting antibody-drug conjugate, in HER3-overexpressing metastatic breast cancer: Updated results from a phase I/II trial. Ann. Oncol. 2019 30 iii48 10.1093/annonc/mdz100.002
    [Google Scholar]
  52. Yu H.A. Yang J.C.H. Hayashi H. Goto Y. Felip E. Reck M. Vigliotti M. Dong Q. Cantero F. Fan P.D. Kanai M. Sternberg D.W. Jänne P.A. HERTHENA-Lung01: A phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. Future Oncol. 2023 19 19 1319 1329 10.2217/fon‑2022‑1250 37212796
    [Google Scholar]
  53. Yu H.A. Goto Y. Hayashi H. Felip E. Chih-Hsin Yang J. Reck M. Yoh K. Lee S.H. Paz-Ares L. Besse B. Bironzo P. Kim D.W. Johnson M.L. Wu Y.L. John T. Kao S. Kozuki T. Massarelli E. Patel J. Smit E. Reckamp K.L. Dong Q. Shrestha P. Fan P.D. Patel P. Sporchia A. Sternberg D.W. Sellami D. Jänne P.A. HERTHENA-Lung01, a phase II trial of Patritumab Deruxtecan (HER3-DXd) in epidermal growth factor receptor–mutated non–small-cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitor therapy and platinum-based chemotherapy. J. Clin. Oncol. 2023 41 35 5363 5375 10.1200/JCO.23.01476 37689979
    [Google Scholar]
  54. Garon E.B. Ciuleanu T.E. Arrieta O. Prabhash K. Syrigos K.N. Goksel T. Park K. Gorbunova V. Kowalyszyn R.D. Pikiel J. Czyzewicz G. Orlov S.V. Lewanski C.R. Thomas M. Bidoli P. Dakhil S. Gans S. Kim J.H. Grigorescu A. Karaseva N. Reck M. Cappuzzo F. Alexandris E. Sashegyi A. Yurasov S. Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): A multicentre, double-blind, randomised phase 3 trial. Lancet 2014 384 9944 665 673 10.1016/S0140‑6736(14)60845‑X 24933332
    [Google Scholar]
  55. Oliveira M. Falato C. Cejalvo J.M. Vila M.M. Tolosa P. Salvador-Bofill F.J. Cruz J. Arumi M. Luna A.M. Guerra J.A. Vidal M. Martínez-Sáez O. Paré L. González-Farré B. Sanfeliu E. Ciruelos E. Espinosa-Bravo M. Pernas S. Izarzugaza Y. Esker S. Fan P.D. Parul P. Santhanagopal A. Sellami D. Villacampa G. Ferrero-Cafiero J.M. Pascual T. Prat A. Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study. Ann. Oncol. 2023 34 8 670 680 10.1016/j.annonc.2023.05.004 37211044
    [Google Scholar]
  56. Yu H.A. Baik C. Kim D.W. Johnson M.L. Hayashi H. Nishio M. Yang J.C.H. Su W.C. Gold K.A. Koczywas M. Smit E.F. Steuer C.E. Felip E. Murakami H. Kim S.W. Su X. Sato S. Fan P.D. Fujimura M. Tanaka Y. Patel P. Sternberg D.W. Sellami D. Jänne P.A. Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC. Ann. Oncol. 2024 35 5 437 447 10.1016/j.annonc.2024.02.003 38369013
    [Google Scholar]
  57. Bourillon L. Bourgier C. Gaborit N. Garambois V. Llès E. Zampieri A. Ogier C. Jarlier M. Radosevic-Robin N. Orsetti B. Delpech H. Theillet C. Colombo P.E. Azria D. Pèlegrin A. Larbouret C. Chardès T. An auristatin‐based antibody‐drug conjugate targeting HER3 enhances the radiation response in pancreatic cancer. Int. J. Cancer 2019 145 7 1838 1851 10.1002/ijc.32273 30882895
    [Google Scholar]
  58. Silva C.M. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene 2004 23 48 8017 8023 10.1038/sj.onc.1208159 15489919
    [Google Scholar]
  59. Spitzner M. Ebner R. Wolff H. Ghadimi B. Wienands J. Grade M. STAT3: A novel molecular mediator of resistance to chemoradiotherapy. Cancers 2014 6 4 1986 2011 10.3390/cancers6041986 25268165
    [Google Scholar]
  60. Camblin A.J. Pace E.A. Adams S. Curley M.D. Rimkunas V. Nie L. Tan G. Bloom T. Iadevaia S. Baum J. Minx C. Czibere A. Louis C.U. Drummond D.C. Nielsen U.B. Schoeberl B. Pipas J.M. Straubinger R.M. Askoxylakis V. Lugovskoy A.A. Dual inhibition of IGF-1R and ErbB3 enhances the activity of Gemcitabine and Nab-Paclitaxel in preclinical models of pancreatic cancer. Clin. Cancer Res. 2018 24 12 2873 2885 10.1158/1078‑0432.CCR‑17‑2262 29549161
    [Google Scholar]
  61. Capone E. Lattanzio R. Gasparri F. Orsini P. Rossi C. Iacobelli V. De Laurenzi V. Natali P.G. Valsasina B. Iacobelli S. Sala G. EV20/NMS-P945, a novel Thienoindole based antibody-drug conjugate targeting HER-3 for solid tumors. Pharmaceutics 2021 13 4 483 10.3390/pharmaceutics13040483 33918158
    [Google Scholar]
  62. Caruso M. Gasparri F. Valsasina B. Albanese C. Beria I. Candiani I. Ciomei M. Colombo N. Cribioli S. Cucchi U. Felder E. Fraietta I. Galvani A. Isacchi A. Marsiglio A. Orsini P. Perego R. Rizzi S. Tomasi A. Troiani S. Visco C. Donati D. Abstract 734: Thienoindoles: New highly promising agents for antibody-drug conjugates generation. Cancer Res. 2018 78 13_Supplement Suppl. 734 10.1158/1538‑7445.AM2018‑734
    [Google Scholar]
  63. Fu Y. Ho M. DNA damaging agent-based antibody-drug conjugates for cancer therapy. Antib. Ther. 2018 1 2 43 53 10.1093/abt/tby007 30294716
    [Google Scholar]
  64. Gandullo-Sánchez L. Capone E. Ocaña A. Iacobelli S. Sala G. Pandiella A. HER3 targeting with an antibody‐drug conjugate bypasses resistance to anti‐HER2 therapies. EMBO Mol. Med. 2020 12 5 e11498 10.15252/emmm.201911498 32329582
    [Google Scholar]
  65. Capone E. Lamolinara A. D’Agostino D. Rossi C. De Laurenzi V. Iezzi M. Iacobelli S. Sala G. EV20-mediated delivery of cytotoxic auristatin MMAF exhibits potent therapeutic efficacy in cutaneous melanoma. J. Control. Release 2018 277 48 56 10.1016/j.jconrel.2018.03.016 29550398
    [Google Scholar]
  66. D’Agostino D. Gentile R. Ponziani S. Di Vittorio G. Dituri F. Giannelli G. Rossi C. Marzullo L. Giansanti F. De Laurenzi V. Iacobelli S. Ippoliti R. Capone E. Sala G. EV20‑sss‑vc/MMAF, an HER‑3 targeting antibody‑drug conjugate displays antitumor activity in liver cancer. Oncol. Rep. 2020 45 2 776 785 10.3892/or.2020.7893 33416143
    [Google Scholar]
  67. Weng W. Meng T. Wang Z. Pan R. Wang M. Chen C. Wang M. Shen Y. AMT-562, a novel HER3-targeting antibody drug conjugate, demonstrates a potential to broaden therapeutic opportunities for HER3-expressing tumors. Mol Cancer Ther. 2023 22 9 1013 10.1158/1535‑7163.MCT‑23‑0198
    [Google Scholar]
  68. Weng W. Meng T. Zhao Q. Shen Y. Fu G. Shi J. Zhang Y. Wang Z. Wang M. Pan R. Ma L. Chen C. Wang L. Zhou B. Zhang H. Pu J. Zhang J. Hu Y.P. Hua G. Qian Y. Liu S.H. Hu W. Meng X. Antibody–Exatecan conjugates with a novel self-immolative moiety overcome resistance in colon and lung cancer. Cancer Discov. 2023 13 4 950 973 10.1158/2159‑8290.CD‑22‑1368 36693125
    [Google Scholar]
  69. Rudnick S.I. Lou J. Shaller C.C. Tang Y. Klein-Szanto A.J.P. Weiner L.M. Marks J.D. Adams G.P. Influence of affinity and antigen internalization on the uptake and penetration of Anti-HER2 antibodies in solid tumors. Cancer Res. 2011 71 6 2250 2259 10.1158/0008‑5472.CAN‑10‑2277 21406401
    [Google Scholar]
  70. Tsumura R. Manabe S. Takashima H. Koga Y. Yasunaga M. Matsumura Y. Influence of the dissociation rate constant on the intra-tumor distribution of antibody-drug conjugate against tissue factor. J. Control. Release 2018 284 49 56 10.1016/j.jconrel.2018.06.016 29906553
    [Google Scholar]
  71. Li X. Yao J. Qu C. Luo L. Li B. Zhang Y. Zhu Z. Qiu Y. Hua H. DB-1310, an ADC comprised of a novel anti-HER3 antibody conjugated to a DNA topoisomerase I inhibitor, is highly effective for the treatment of HER3-positive solid tumors. J. Transl. Med. 2024 22 1 362 10.1186/s12967‑024‑05133‑7 38632563
    [Google Scholar]
  72. Haikala H.M. Lopez T. Köhler J. Eser P.O. Xu M. Zeng Q. Teceno T.J. Ngo K. Zhao Y. Ivanova E.V. Bertram A.A. Leeper B.A. Chambers E.S. Adeni A.E. Taus L.J. Kuraguchi M. Kirschmeier P.T. Yu C. Shiose Y. Kamai Y. Qiu Y. Paweletz C.P. Gokhale P.C. Jänne P.A. EGFR Inhibition enhances the cellular uptake and antitumor-activity of the HER3 antibody–drug conjugate HER3–DXd. Cancer Res. 2022 82 1 130 141 10.1158/0008‑5472.CAN‑21‑2426 34548332
    [Google Scholar]
  73. Pander G. Uhl P. Kühl N. Haberkorn U. Anderl J. Mier W. Antibody–drug conjugates: What drives their progress? Drug Discov. Today 2022 27 10 103311 10.1016/j.drudis.2022.06.011 35787480
    [Google Scholar]
  74. Gerber H.P. Sapra P. Loganzo F. May C. Combining antibody–drug conjugates and immune-mediated cancer therapy: What to expect? Biochem. Pharmacol. 2016 102 1 6 10.1016/j.bcp.2015.12.008 26686577
    [Google Scholar]
  75. Tsuchikama K. Anami Y. Ha S.Y.Y. Yamazaki C.M. A phase 2 study of HER3-DXd in patients (pts) with metastatic breast cancer (MBC). JCO 2016 41 1004
    [Google Scholar]
  76. Tsuchikama K. Anami Y. Ha S.Y.Y. Yamazaki C.M. Exploring the next generation of antibody–drug conjugates. Nat. Rev. Clin. Oncol. 2024 21 3 203 223 10.1038/s41571‑023‑00850‑2 38191923
    [Google Scholar]
  77. Maiti R. Patel B. Patel N. Patel M. Patel A. Dhanesha N. Antibody drug conjugates as targeted cancer therapy: Past development, present challenges and future opportunities. Arch. Pharm. Res. 2023 46 5 361 388 10.1007/s12272‑023‑01447‑0 37071273
    [Google Scholar]
  78. Fosdahl A.M. Dietrich M. Schink K.O. Malik M.S. Skeie M. Bertelsen V. Stang E. ErbB3 interacts with Hrs and is sorted to lysosomes for degradation. Biochim. Biophys. Acta Mol. Cell Res. 2017 1864 12 2241 2252 10.1016/j.bbamcr.2017.08.011 28867611
    [Google Scholar]
  79. Offterdinger M. Schöfer C. Weipoltshammer K. Grunt T.W. c-erbB-3 : A nuclear protein in mammary epithelial cells J. Cell Biol. 2002 157 6 929 940 10.1083/jcb.200109033 12045181
    [Google Scholar]
  80. Black L.E. Longo J.F. Carroll S.L. Mechanisms of receptor tyrosine-protein kinase ErbB-3 (ERBB3) action in human neoplasia. Am. J. Pathol. 2019 189 10 1898 1912 10.1016/j.ajpath.2019.06.008 31351986
    [Google Scholar]
  81. Prasetyanti P.R. Capone E. Barcaroli D. D’Agostino D. Volpe S. Benfante A. van Hooff S. Iacobelli V. Rossi C. Iacobelli S. Medema J.P. De Laurenzi V. Sala G. ErbB-3 activation by NRG-1β sustains growth and promotes vemurafenib resistance in BRAF-V600E colon cancer stem cells (CSCs). Oncotarget 2015 6 19 16902 16911 10.18632/oncotarget.4642 26160848
    [Google Scholar]
  82. Aurisicchio L. Marra E. Roscilli G. Mancini R. Ciliberto G. The promise of anti-ErbB3 monoclonals as new cancer therapeutics. Oncotarget 2012 3 8 744 758 10.18632/oncotarget.550 22889873
    [Google Scholar]
  83. Conradi L.C. Spitzner M. Metzger A.L. Kisly M. Middel P. Bohnenberger H. Gaedcke J. Ghadimi M.B. Liersch T. Rüschoff J. Beißbarth T. König A. Grade M. Combined targeting of HER-2 and HER-3 represents a promising therapeutic strategy in colorectal cancer. BMC Cancer 2019 19 1 880 10.1186/s12885‑019‑6051‑0 31488078
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673358929250213093803
Loading
HER3-targeting Antibody-drug Conjugates Therapy for Solid Tumors: Recent Advances and Future Potentials
Bentham Science Publishers ; https://doi.org/10.2174/0109298673358929250213093803
/content/journals/cmc/10.2174/0109298673358929250213093803
/content/journals/cmc/10.2174/0109298673358929250213093803
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Human epidermal growth factor receptor 3 (HER3) ; HER3-targeting ADCs ; antibody-drug conjugates (ADC) ; targeted therapy ; solid tumors ; U3-1402) ; patritumab deruxtecan (HER3-DXd

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