ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2025
Assessing efficacy of anti-glypican-1 antibody-drug conjugate as potential therapeutic approach for gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Chimeric Anti-Glypican 1 Antibodies Exert Antitumor Activities in Xenograft Models of Lung and Pancreatic Cancers.International journal of molecular sciences · 2026Article
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10 authors.
Funding
Abstract
backgroundDespite significant advancements in cancer treatment, gastric cancer (GC) continues to have a high incidence and mortality rate. Antibody-drug conjugates (ADCs) are emerging as a viable treatment option for GC. Glypican-1 (GPC1), a cell surface proteoglycan, has garnered interest for its role in tumor growth and its potential as a biomarker. This study evaluated the efficacy of an ADC comprising a humanized anti-GPC1 monoclonal antibody conjugated with monomethyl auristatin E (GPC1-ADC) to target GPC1 in GC.
methodsGPC1 expression was assessed in GC cell lines and tissues. The cytotoxic efficacy and mechanism of action of GPC1-ADC were evaluated through comprehensive in vitro assays. In vivo efficacy was further assessed in xenograft mouse models, focusing on tumor growth inhibition and its performance against peritoneal dissemination.
resultsIn vitro, GPC1-ADC exhibited significant cytotoxicity against GPC1-positive cell lines by inducing cell cycle arrest and apoptosis. Additionally, GPC1-ADC demonstrated promising bystander-killing activity via cancer-associated fibroblasts, highlighting its potential to target the heterogeneous tumor microenvironment characteristic of GC. In vivo, GPC1-ADC significantly inhibited tumor growth and demonstrated substantial therapeutic effects in a peritoneal dissemination model. Immunohistochemical analysis of tumor specimens from GC patients revealed that 90.2% of differentiated types and 66.7% of poorly differentiated types exhibited high GPC1 expression. High GPC1 expression in tumor samples was significantly associated with poorer progression-free and overall survival.
conclusionsOur findings suggest that GPC1-targeting ADCs represent a promising therapeutic option for GPC1-positive GC.
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