Progress of Clinical Studies Targeting Claudin18.2 for the Treatment of Gastric Cancer

Claudin18.2 is a tight junction protein, highly selective, generally expressed only in normal gastric mucosal epithelial cells, which can effectively maintain the polarity of epithelial and endothelial cells, thus effectively regulating the permeability and conductance of the paracellular pathway. A...

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Bibliographic Details
Published in:Digestive diseases and sciences 2024-07, Vol.69 (7), p.2631-2647
Main Authors: Jin, Wu-mei, Zhu, Yan, Cai, Zhi-qiang, He, Na, Yu, Zhi-qiong, Li, Shuang, Yang, Ji-yuan
Format: Article
Language:English
Subjects:
Animals
Antibodies - immunology
Antibodies - therapeutic use
Antineoplastic Agents - therapeutic use
Biochemistry
Claudins - immunology
Claudins - metabolism
Clinical Trials as Topic
Gastric cancer
Gastroenterology
Hepatology
Humans
Immunotherapy
Medicine
Medicine & Public Health
Metastasis
Molecular Targeted Therapy - methods
Oncology
Original Article
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Stomach Neoplasms - therapy
Transplant Surgery
Tumors
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Summary:Claudin18.2 is a tight junction protein, highly selective, generally expressed only in normal gastric mucosal epithelial cells, which can effectively maintain the polarity of epithelial and endothelial cells, thus effectively regulating the permeability and conductance of the paracellular pathway. Abnormal expression of Claudin18.2 can occur in various primary malignant tumors, especially gastrointestinal tumors, and even in metastatic foci. It regulates its expression by activating the aPKC/MAPK/AP-1 pathway, and therefore, the Claudin18.2 protein is a pan-cancer target expressed in primary and metastatic lesions in human cancer types. Zolbetuximab (IMAB362), an antibody specific for Claudin18.2, has been successfully tested in a phase III clinical trial, and the results of the study showed that combining Zolbetuximab with chemotherapy notably extends patients’ survival and is expected to be a potential first-line treatment for patients with Claudin18.2(+)/HER-2(−) gastric cancer. Here, we systematically describe the biological properties and oncogenic effects of Claudin18.2, centering on its clinical-pathological aspects and the progress of drug studies in gastric cancer, which can help to further explore its clinical value.
ISSN:0163-2116
1573-2568
1573-2568
DOI:10.1007/s10620-024-08435-4