Claudin-18.2: Why Claudin-18.2 expression matters
“Claudin-18.2 is not expressed in normal tissues outside the stomach, I mean that its expression is highly restricted to the normal gastric epithelial cells lining the stomach in physiological conditions.
This is unlike many other biomarkers, which may be found in a wide variety of normal tissues, potentially leading to off-target effects in therapy.
Here’s why this matters:
Tissue-Specific Expression:
Claudin-18.2 is specifically expressed in the tight junctions of gastric epithelial cells. In healthy individuals, it is not detectable in the epithelial cells of other organs, such as the intestines, liver, pancreas, or other normal tissues, under non-disease conditions.
Therapeutic Advantage:
Because Claudin-18.2 is confined to the stomach lining in normal tissues, therapies targeting it (e.g., Zolbetuximab) are highly specific to gastric cancer cells, minimizing damage to normal, healthy tissues.
This specificity reduces the risk of off-target toxicity, a common challenge in cancer therapy.
Metastatic Tumors:
Even in metastatic gastric cancer, Claudin-18.2 often continues to be expressed, providing a reliable target for systemic therapies.
However, in cancerous or metaplastic conditions, its expression pattern can become dysregulated and show up in tumors derived from gastric epithelium, which is why it serves as an excellent biomarker for diagnosing and targeting gastric cancer.”
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