CLDN18

CLDN18 is a gene that encodes the protein Claudin-18, which is a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junctions are specialized regions of cell-to-cell contact that are particularly abundant in epithelial cells and are essential for maintaining the polarity and integrity of these cells, thereby regulating the passage of molecules in the intercellular space.

Function

Claudin-18 plays a critical role in the formation and maintenance of tight junctions in the epithelium of the stomach and lungs. It exists in two isoforms, CLDN18.1 and CLDN18.2, due to alternative splicing. CLDN18.1 is primarily expressed in the lung, while CLDN18.2 is predominantly found in the gastric epithelium. The specific localization of Claudin-18 in these tissues suggests its importance in maintaining the barrier and transport functions of the gastric and pulmonary epithelia.

Clinical Significance

Alterations in the expression or function of CLDN18 have been implicated in several diseases. In the stomach, aberrant expression of CLDN18.2 has been associated with gastric cancer, making it a potential target for cancer therapy. The disruption of tight junctions, including those formed by Claudin-18, can lead to increased permeability and may contribute to the pathogenesis of various diseases, including inflammatory bowel disease (IBD) and asthma in the lungs.

Therapeutic Target

Given its restricted expression pattern and involvement in disease, CLDN18.2 has emerged as a promising target for cancer therapy, particularly in gastric cancer. Antibodies targeting CLDN18.2, such as zolbetuximab, are currently under investigation in clinical trials for their potential to treat CLDN18.2-positive gastric cancers. These therapies aim to specifically target and kill cancer cells expressing CLDN18.2, while sparing normal cells, thereby offering a more selective and potentially less toxic treatment option compared to conventional chemotherapy.

Research

Research on CLDN18 continues to explore its function, regulation, and role in disease. Understanding the molecular mechanisms governing the expression and function of Claudin-18 isoforms could provide insights into the pathogenesis of diseases affecting the stomach and lungs and lead to the development of novel therapeutic strategies.