In the process of solid tumor transformation, the expression of claudins is often dysregulated. Claudins are involved in almost all aspects of tumor biology and steps of tumor development, suggesting that they have the potential to be diagnostics, and prognostic biomarkers and therapeutic targets. Current studies have found that Claudin18.2 is overexpressed in gastric cancer, pancreatic cancer, ovarian cancer and other diseases. Targeted anti-tumor therapy based on Claudin 18.2 has become a research hotspot recently. Therefore, this article reviews the basic structural characteristics of Claudin18.2, its expression in various malignant solid tumors, the progress of research and application, and prospect.
ObjectiveTo systematically review the current clinical research status of major therapeutic targets and research advances in emerging targets for targeted therapy in advanced gastric cancer, so as to provide a reference for clinical precision therapy. MethodThe key studies on major therapeutic targets for targeted therapy are reviewed, including HER2 (human epidermal growth factor receptor 2), VEGFR2 (vascular endothelial growth factor receptor 2), Claudin 18.2, FGFR2b (fibroblast growth factor receptor 2b), DKK1 (Dickkopf-related protein 1), and MET (mesenchymal to epithelial transition) factor. ResultsClinical research and application of anti-HER2 agents have been well established, and such agents have been utilized throughout the entire course from the first-line to later-line therapy. VEGFR2 inhibitors have been positioned as core treatments in the second-line and subsequent-line settings. The emergence of targeted therapy against Claudin 18.2 has provided the new first-line option for patients with HER2-negative advanced gastric cancer. Investigations into agents targeting targets, including FGFR2b, DKK1, and MET, have been continuously intensified. Conclusions Currently, survival of patients with advanced gastric cancer can be improved by targeted therapy. However, several challenges remain to be addressed, including heterogeneous target expression, complex resistance mechanisms, and uncertainty regarding the optimal treatment strategy. Further investigations are warranted in dynamic monitoring and standardization of target detection, clarification of resistance mechanisms and optimization of combination strategies, as well as sequencing of therapeutic agents and individualized treatment selection.
