[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-355642-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-355642-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","pertuzumab-enhances-the-antitumor-activity-of-t-dxd-in-her2-positive-gastric-cancer-cells","Pertuzumab Enhances the Antitumor Activity of T-DXd in HER2-Positive Gastric Cancer Cells","","Pertuzumab enhances the antitumor activity of trastuzumab deruxtecan (T-DXd) in HER2-positive gastric cancer cells by addressing HER2–HER3 signaling. Preclinical in vitro and in vivo data evaluate T-DXd efficacy across HER2-expressing cell lines, show that high membrane HER2 expression predicts response, and identify synergy between pertuzumab and T-DXd in specific HER2–HER3 dimer contexts. NRG1 stimulation attenuates T-DXd effects, with partial reversal by pertuzumab in NCI-N87 but not OE19.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/pertuzumab-enhances-the-antitumor-activity-of-t-dxd-in-her2-positive-gastric-cancer-cells/355642/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/pertuzumab-enhances-the-antitumor-activity-of-t-dxd-in-her2-positive-gastric-cancer-cells/355642.png","ImageObject",300,407,{"name":42,"@type":43},"นรินทร์","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What therapeutic rationale supports combining T-DXd with pertuzumab in HER2-positive gastric cancer?","Question",{"text":63,"@type":64},"The study targets both HER2 and HER3 pathways, aiming to disrupt HER2–HER3 heterodimerization while leveraging T-DXd’s HER2-selective delivery of a cytotoxic payload.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does HER2 expression relate to T-DXd efficacy in the tested cell lines?",{"text":68,"@type":64},"In vitro results indicate that T-DXd efficacy correlates with high levels of membrane HER2 expression, and the most effective proliferation inhibition is observed in HER2 3+ lines such as NCI-N87 and OE19.",{"name":70,"@type":61,"acceptedAnswer":71},"What is the impact of NRG1 stimulation and how does pertuzumab modify it?",{"text":72,"@type":64},"NRG1 stimulation attenuates the antiproliferative effect of T-DXd; this attenuation is partially reversed by adding pertuzumab in NCI-N87 but not in OE19.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},355642,1790143694,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},2336475104957,"https://ap-avatar.wpscdn.com/avatar/22000c4c6bd8a5076e1?x-image-process=image/resize,m_fixed,w_180,h_180&k=1787554080175789136","Pertuzumab Enhances the Antitumor Activity of T-DXd in HER2-Positive Gastric Cancer Cells  \nMinsu Kang1,2, Kui-Jin Kim3, Hyeon Jeong Oh4, Ji Hea Sung2, Milang Nam2, Bo-Ram Park2, Sung-Hyun Hwang3, Eun Hee Jung2, Koung Jin Suh2, Ji-Won Kim2, Se Hyun Kim2, Jin Won Kim2, Yu Jung Kim2, Jee Hyun Kim2, and Keun-Wook Lee1,2  \n|  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n|  | For HER2-positive advanced gastric cancer, a recent major therapeutic advancement is the development of trastuzumab deruxtecan (T-DXd), a HER2-directed antibody–drug conjugate. In this disease, simultaneously targeting HER2 and HER3 pathways has the potential to be a promising therapeutic strategy. However, the therapeutic approach of combining T-DXd with pertuzumab, which disrupts HER2–HER3 heterodimerization, has not yet been explored in gastric cancer, making this study a pioneering effort. In vitro, T-DXd efficacy correlated with high levels of membrane HER2 expression. Among the 12 cell lines tested, two cell lines (NCI-N87 and OE19) confirmed as HER2 3+ by IHC showed the most effective proliferation inhibition by T-DXd. When comparing NCI-N87 and OE19, HER2– HER3 dimerization was found to be more abundant in NCI-N87, and combination treatment with pertuzumab and T-DXd showed synergy\u003Cbr>􀀶 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | in cell growth inhibition in NCI-N87 but not in OE19. NRG1 stimulation attenuated the antiproliferative effect of T-DXd. This attenuation ofT-DXd activity by NRG1 was partially reversed by the addition ofpertuzumab in NCI-N87 but not in OE19. Notably, the combination of T-DXd and pertuzumab enhanced membrane HER2 internalization more effectively in NCI-N87 than in OE19. In vivo mouse experiments using NCI-N87 cells showed the combination treatment significantly suppressed tumor growth compared with either monotherapy. Taken together, our findings suggest that dual targeting of HER2 and HER3 with T-DXd and pertuzumab may improve therapeutic outcomes in HER2-positive gastric cancer, particularly in tumors enriched with HER2–HER3 heterodimers. These preclinical data provide strong rationale for clinical trials evaluating this combination strategy in HER2-positive gastric cancer. |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n\nIntroduction  \nGastric cancer is a serious global health challenge and is the fifth most common malignancy and the fourth leading cause of cancerrelated deaths worldwide (1). HER2 amplification is a key molecular characteristic of a subset of gastric cancer cases, constituting 7% to 34% of all gastric adenocarcinomas (2) . The introduction of HER2-targeted therapies, particularly the mAb trastuzumab, in combination with chemotherapy, has improved patient survival (2) .  \nTrastuzumab deruxtecan (T-DXd), an innovative antibody–drug conjugate (ADC), marks a significant advancement in HER2-positive gastric cancer therapy. By linking trastuzumab to topoisomerase 1 (T","cbCaiaAcobJfwAsN","https://ap.wps.com/l/cbCaiaAcobJfwAsN","pdf",9781820,13,"English","# Introduction\n## HER2 amplification and HER2-targeted therapy background\n## Trastuzumab deruxtecan (T-DXd) design and clinical rationale","[{\"question\":\"What therapeutic rationale supports combining T-DXd with pertuzumab in HER2-positive gastric cancer?\",\"answer\":\"The study targets both HER2 and HER3 pathways, aiming to disrupt HER2–HER3 heterodimerization while leveraging T-DXd’s HER2-selective delivery of a cytotoxic payload.\"},{\"question\":\"How does HER2 expression relate to T-DXd efficacy in the tested cell lines?\",\"answer\":\"In vitro results indicate that T-DXd efficacy correlates with high levels of membrane HER2 expression, and the most effective proliferation inhibition is observed in HER2 3+ lines such as NCI-N87 and OE19.\"},{\"question\":\"What is the impact of NRG1 stimulation and how does pertuzumab modify it?\",\"answer\":\"NRG1 stimulation attenuates the antiproliferative effect of T-DXd; this attenuation is partially reversed by adding pertuzumab in NCI-N87 but not in OE19.\"}]","Pertuzumab Enhances the Antitumor Activity of T-DXd in HER2-Positive Gastric Cancer Cells | PDF",1790120261,33]