{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:54:13Z","timestamp":1791975253710,"version":"4.4.0"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ck0106650"],"award-info":[{"award-number":["JP21ck0106650"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ck0106912"],"award-info":[{"award-number":["JP24ck0106912"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K07240"],"award-info":[{"award-number":["JP22K07240"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K10568"],"award-info":[{"award-number":["JP25K10568"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp;amp; Neck"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral squamous cell carcinoma (OSCC) is a major health concern with limited therapeutic options. Glypican\u20101 (GPC1), a heparan sulphate proteoglycan, has been implicated in several malignancies; however, its therapeutic role in OSCC remains elusive. This study investigated the potential of a novel glypican\u20101 antibody\u2013drug conjugate (GPC1\u2010ADC) conjugated with monomethyl auristatin E as a therapeutic strategy for OSCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GPC1 expression in OSCC tissues was examined by immunohistochemistry using tissue microarrays and by western blotting in OSCC cell lines. The cytotoxicity of GPC1\u2010ADC was assessed using in\u00a0vitro viability assays, and its effects on the cell cycle and apoptosis were analyzed using flow cytometry and caspase\u20103\/7 activity assays. In\u00a0vivo antitumor efficacy was evaluated using OSCC cell line\u2013derived and patient\u2010derived xenograft (PDX) mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High GPC1 expression was observed in 78% (39\/50) of OSCC cases, whereas normal oral tissues showed no detectable expression. Western blotting confirmed GPC1 protein expression in all the OSCC cell lines tested. GPC1\u2010ADC markedly reduced cell viability in a dose\u2010dependent manner (IC5\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u20090.053\u20130.117\u2009nM), induced G2\/M\u2010phase arrest, and activated caspase\u20103\/7, indicating apoptosis. In\u00a0vivo, high\u2010dose GPC1\u2010ADC markedly inhibited tumor growth in both xenograft and PDX models compared with control treatments, without causing weight loss.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GPC1\u2010ADC demonstrated potent and specific antitumor activity against GPC1\u2010expressing OSCC in\u00a0vitro and in\u00a0vivo. These findings suggest that GPC1\u2010ADC is a promising therapeutic candidate for OSCC and may provide a basis for new treatment strategies; however, further preclinical and clinical evaluation is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70514","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:40:49Z","timestamp":1791974449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glypican\u20101\u2010Targeted Antibody\u2013Drug Conjugate Exhibits Antitumor Effects Against Oral Squamous Cell Carcinoma"],"prefix":"10.1002","author":[{"given":"Kengo","family":"Obata","sequence":"first","affiliation":[{"name":"Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery School of Dentistry, Iwate Medical University  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-9009","authenticated-orcid":false,"given":"Satoshi","family":"Serada","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery and Medical Device Development Institute for Biomedical Sciences, Iwate Medical University  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-340X","authenticated-orcid":false,"given":"Yuji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery and Medical Device Development Institute for Biomedical Sciences, Iwate Medical University  Yahaba Iwate Japan"},{"name":"Division of Allergy and Rheumatology, Department of Internal Medicine Iwate Medical University School of Medicine  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Tuchida","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Iwate Medical University School of Medicine  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Miyaguchi","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Iwate Medical University School of Medicine  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Funajima","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery and Medical Device Development Institute for Biomedical Sciences, Iwate Medical University  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-6095","authenticated-orcid":false,"given":"Hiroyuki","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery School of Dentistry, Iwate Medical University  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Naka","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery and Medical Device Development Institute for Biomedical Sciences, Iwate Medical University  Yahaba Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"issue":"3","key":"e_1_2_12_2_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: a Cancer Journal for Clinicians"},{"issue":"3","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ctrv.2013.09.007","article-title":"Targeted Therapies for Squamous Cell Carcinoma of the Head and Neck: Current Knowledge and Future Directions","volume":"40","author":"Schmitz S.","year":"2014","journal-title":"Cancer Treatment Reviews"},{"issue":"19","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for Recurrent Squamous\u2010Cell Carcinoma of the Head and Neck","volume":"375","author":"Ferris R. L.","year":"2016","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/bjc.2016.183","article-title":"Overexpression of Glypican\u20101 Implicates Poor Prognosis and Their Chemoresistance in Oesophageal Squamous Cell Carcinoma","volume":"115","author":"Hara H.","year":"2016","journal-title":"British Journal of Cancer"},{"issue":"4","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1172\/JCI200113712","article-title":"Glypicans: Proteoglycans With a Surprise","volume":"108","author":"Filmus J.","year":"2001","journal-title":"Journal of Clinical Investigation"},{"issue":"9","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1172\/JCI4105","article-title":"The Cell\u2010Surface Heparan Sulfate Proteoglycan Glypican\u20101 Regulates Growth Factor Action in Pancreatic Carcinoma Cells and Is Overexpressed in Human Pancreatic Cancer","volume":"102","author":"Kleeff J.","year":"1998","journal-title":"Journal of Clinical Investigation"},{"issue":"9","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"828","DOI":"10.18632\/oncotarget.27492","article-title":"Glypican\u20101 in Human Glioblastoma: Implications in Tumorigenesis and Chemotherapy","volume":"11","author":"Listik E.","year":"2020","journal-title":"Oncotarget"},{"issue":"1","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/2044-5040-4-5","article-title":"Glypican\u20101 Regulates Myoblast Response to HGF via Met in a Lipid Raft\u2010Dependent Mechanism: Effect on Migration of Skeletal Muscle Precursor Cells","volume":"4","author":"Gutierrez J.","year":"2014","journal-title":"Skeletal Muscle"},{"issue":"9","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1038\/s41416-020-0781-2","article-title":"Anti\u2010Glypican\u20101 Antibody\u2010Drug Conjugate Is a Potential Therapy Against Pancreatic Cancer","volume":"122","author":"Nishigaki T.","year":"2020","journal-title":"British Journal of Cancer"},{"issue":"9","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1158\/1535-7163.MCT-21-0015","article-title":"Anti\u2010Glypican\u20101 Antibody\u2010Drug Conjugate as Potential Therapy Against Tumor Cells and Tumor Vasculature for Glypican\u20101\u2010Positive Cholangiocarcinoma","volume":"20","author":"Yokota K.","year":"2021","journal-title":"Molecular Cancer Therapeutics"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s10120-025-01647-1","article-title":"Assessing Efficacy of Anti\u2010Glypican\u20101 Antibody\u2010Drug Conjugate as Potential Therapeutic Approach for Gastric Cancer","volume":"28","author":"Suzuki Y.","year":"2025","journal-title":"Gastric Cancer"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.wneu.2017.05.165","article-title":"High Expression of Glypican\u20101 Predicts Dissemination and Poor Prognosis in Glioblastomas","volume":"105","author":"Saito T.","year":"2017","journal-title":"World Neurosurgery"},{"issue":"15","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"24741","DOI":"10.18632\/oncotarget.15799","article-title":"Glypican\u20101 Targeted Antibody\u2010Based Therapy Induces Preclinical Antitumor Activity Against Esophageal Squamous Cell Carcinoma","volume":"8","author":"Harada E.","year":"2017","journal-title":"Oncotarget"},{"issue":"9","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.neo.2021.07.006","article-title":"A Glypican\u20101\u2010Targeted Antibody\u2010Drug Conjugate Exhibits Potent Tumor Growth Inhibition in Glypican\u20101\u2010Positive Pancreatic Cancer and Esophageal Squamous Cell Carcinoma","volume":"23","author":"Munekage E.","year":"2021","journal-title":"Neoplasia"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"100982","DOI":"10.1016\/j.neo.2024.100982","article-title":"Glypican\u20101\u2010Targeted Antibody\u2010Drug Conjugate Inhibits the Growth of Glypican\u20101\u2010Positive Glioblastoma","volume":"50","author":"Uchida S.","year":"2024","journal-title":"Neoplasia"},{"issue":"5","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/ijc.31124","article-title":"Anti\u2010Glypican\u20101 Antibody\u2010Drug Conjugate Exhibits Potent Preclinical Antitumor Activity Against Glypican\u20101 Positive Uterine Cervical Cancer","volume":"142","author":"Matsuzaki S.","year":"2018","journal-title":"International Journal of Cancer"},{"issue":"14","key":"e_1_2_12_18_1","first-page":"5562","article-title":"Glypican\u20101 Is Overexpressed in Human Breast Cancer and Modulates the Mitogenic Effects of Multiple Heparin\u2010Binding Growth Factors in Breast Cancer Cells","volume":"61","author":"Matsuda K.","year":"2001","journal-title":"Cancer Research"},{"issue":"1","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1186\/s12885-022-09898-2","article-title":"Tumor Specificity of WNT Ligands and Receptors Reveals Universal Squamous Cell Carcinoma Oncogenes","volume":"22","author":"Chen C.","year":"2022","journal-title":"BMC Cancer"},{"issue":"4","key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"e26100","DOI":"10.1016\/j.heliyon.2024.e26100","article-title":"A Novel Lysosome\u2010Related Prognostic Signature Associated With Prognosis and Immune Infiltration Landscape in Oral Squamous Cell Carcinoma","volume":"10","author":"Liu J. J.","year":"2024","journal-title":"Heliyon"},{"issue":"5","key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/PAI.0000000000000907","article-title":"Glypican\u20101, \u22123, \u22125 (GPC1, GPC3, GPC5) and Hedgehog Pathway Expression in Oral Squamous Cell Carcinoma","volume":"29","author":"Schlaepfer Sales C. B.","year":"2021","journal-title":"Applied Immunohistochemistry & Molecular Morphology"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.70514","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hed.70514","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.70514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:40:52Z","timestamp":1791974452000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.70514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":20,"alternative-id":["10.1002\/hed.70514"],"URL":"https:\/\/doi.org\/10.1002\/hed.70514","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hed.70514"}}