Emerging evidence of targeting non-oncogenic drivers for gastric cancer: Claudin18.2 and beyond

Human epidermal growth factor receptor 2 was the first successful molecular target in treating gastric cancer, marking a significant milestone for targeted therapies. Emerging evidence on Claudin18.2 (CLDN18.2) has recently reshaped the paradigm of therapeutic targets, expanding the focus beyond con...

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Bibliographic Details
Main Authors: Kazumasa Yamamoto, Izuma Nakayama, Kohei Shitara
Format: Article
Language:English
Published: SAGE Publishing 2025-06-01
Series:Therapeutic Advances in Medical Oncology
Online Access:https://doi.org/10.1177/17588359251344804
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Summary:Human epidermal growth factor receptor 2 was the first successful molecular target in treating gastric cancer, marking a significant milestone for targeted therapies. Emerging evidence on Claudin18.2 (CLDN18.2) has recently reshaped the paradigm of therapeutic targets, expanding the focus beyond conventional oncogenic drivers. Therapeutic strategies now target tumor-associated molecules which highly expressed in tumors but are not necessarily critical for tumor growth or survival. Molecules such as trophoblast cell surface antigen 2, Caprin-1, and Nectin-4 are promising non-oncogenic targets for advanced gastric cancer treatment. Innovative therapeutic approaches, such as antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy, have accelerated the potential of targeting tissue-associated antigens. This review provides an update on CLDN18.2-directed therapies and explores the development of novel therapeutic strategies targeting non-oncogenic drivers. In addition, we discuss ongoing challenges, including biomarker overlap, resistance mechanisms, and future directions for next-generation molecular targeted therapy in gastric cancer.
ISSN:1758-8359