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Future Landscape of Anti-Claudin 18.2 Antibodies in Gastric Adenocarcinoma
Wendy M Covert1, Jane E Rogers1
1Department of Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
Advanced gastric adenocarcinoma (GAC) carries a poor prognosis. Targeted therapy in GAC has traditionally been limited to anti-human epidermal growth factor receptor-2 and anti-vascular endothelial growth factor agents. Recent years have brought immune checkpoint therapy to the GAC treatment landscape. However, continued discovery of targeted therapy in GAC is needed. Claudins, transmembrane proteins located in tight junctions of epithelial and endothelial cells, help regulate cellular polarity. Claudin dysregulation has been linked to cancers and other diseases. Claudin 18.2 specifically has become a new novel and exciting biomarker for GAC. Many agents are in the investigative pipeline, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric T-cell therapy. Recently, zolbetuximab, an anti-claudin 18.2 monoclonal antibody, was the first of these agents to get FDA approval. Here, we review zolbetuximab's place in therapy along with other agents being explored.
Insights
Zolbetuximab, an anti-claudin 18.2 antibody, is the first targeted therapy approved for advanced gastric adenocarcinoma (GAC). This review covers its role and other novel claudin 18.2 agents in GAC treatment.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Advanced gastric adenocarcinoma (GAC) has a poor prognosis, with limited targeted therapy options.
- Claudin 18.2 is a novel biomarker identified in GAC, offering new therapeutic avenues.
- Dysregulation of claudins, transmembrane proteins, is implicated in various cancers.
Purpose of the Study:
- To review the therapeutic landscape of targeted therapies for advanced gastric adenocarcinoma.
- To discuss the role of zolbetuximab, an anti-claudin 18.2 antibody, in GAC treatment.
- To explore other emerging claudin 18.2-targeted agents.
Main Methods:
- Literature review of targeted therapies for advanced gastric adenocarcinoma.
- Analysis of clinical data and research on claudin 18.2 as a biomarker.
- Evaluation of investigational agents including monoclonal antibodies, antibody-drug conjugates, and cell therapies.
Main Results:
- Zolbetuximab, an anti-claudin 18.2 monoclonal antibody, has received FDA approval for GAC.
- Several other claudin 18.2-targeted agents are in various stages of clinical investigation.
- Immune checkpoint inhibitors have also entered the GAC treatment paradigm.
Conclusions:
- Claudin 18.2 represents a significant advancement in targeted therapy for GAC.
- Zolbetuximab offers a new treatment option, with ongoing research into other claudin 18.2-based therapies.
- Continued research is crucial for improving outcomes in advanced gastric adenocarcinoma.
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