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Emerging claudin-18.2 antagonists in the treatment of biliary tract cancer
Daniel Neureiter1,2, Dino Bekric1,2, Christian Mayr3,4
1Institute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), Salzburg, Austria.
Introduction:
The tight junction protein Claudin-18.2 (CLDN-18.2) has been identified as a novel drug target for various solid tumors, including biliary tract cancers (BTC). Antibody-based approaches to target CLDN-18.2 have shown promising results in early clinical trials and several novel modalities like antibody-drug conjugates, bispecific T-cell engagers or CAR T-cells are currently also explored.
Areas Covered:
This review discusses the translational knowledge and gaps related to the underrepresentation of BTC in early clinical (basket) studies. We outline the current status of early clinical trials of drugs targeting CLDN-18.2 in BTC and discuss the need to determine prevalence and cutoff data in larger cohorts to overcome limitations related to clinical and molecular heterogeneity of BTC.
Expert Opinion:
Targeting CLDN-18.2 is a promising novel approach to treat solid tumors, including BTC. To confirm encouraging first clinical data, larger studies specific for BTC are needed to address tumor heterogeneity and to determine cutoff levels of CLDN-18.2 expression. Such studies are also needed to understand combination options and sequencing of therapies and to further validate novel approaches to fully exploit the potential of targeting CLDN-18.2 in BTC.
Insights
Claudin-18.2 (CLDN-18.2) shows promise as a cancer drug target, especially for biliary tract cancers (BTC). Further research is needed to confirm its effectiveness in larger, BTC-specific studies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Claudin-18.2 (CLDN-18.2) is a novel drug target for solid tumors, including biliary tract cancers (BTC).
- Antibody-based therapies targeting CLDN-18.2 have demonstrated early clinical success.
- Emerging modalities include antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cells.
Purpose of the Study:
- To review translational knowledge and identify gaps concerning BTC underrepresentation in early clinical trials.
- To outline the current status of CLDN-18.2-targeted therapies in BTC clinical trials.
- To discuss the necessity of determining CLDN-18.2 prevalence and cutoff data in larger cohorts.
Main Methods:
- Review of existing literature and clinical trial data.
- Analysis of translational knowledge gaps.
- Discussion of clinical and molecular heterogeneity in BTC.
Main Results:
- CLDN-18.2 is a promising target for solid tumors, particularly BTC.
- Early clinical trials show encouraging results for CLDN-18.2-targeted therapies.
- Limitations exist due to clinical and molecular heterogeneity of BTC.
Conclusions:
- Larger, BTC-specific studies are required to validate early clinical data.
- Determining CLDN-18.2 expression prevalence and cutoff levels is crucial.
- Further research should explore combination therapies and novel treatment strategies to maximize CLDN-18.2 targeting potential in BTC.
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