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Updated: Jun 12, 2025

Three-Dimensional Culture of Murine Colonic Crypts to Study Intestinal Stem Cell Function Ex Vivo
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Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review)

Masuko Katoh1, Masaru Katoh1

  • 1Department of Global Network, M & M Precision Medicine, Tokyo 113‑0033, Japan.

International Journal of Molecular Medicine
|September 20, 2024
PubMed

Insights

Claudins (CLDNs) are crucial in cancer, leading to CLDN-targeting therapies like monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs). CLDN18.2-targeting treatments show promise in gastric cancer clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Claudins (CLDNs) are tetraspan-transmembrane proteins forming tight junctions.
  • Specific CLDN isoforms (e.g., CLDN6, CLDN18.2) are upregulated in human cancers.
  • This upregulation presents therapeutic targets for cancer treatment.

Purpose of the Study:

  • To review investigational drugs targeting CLDN1, CLDN4, CLDN6, and CLDN18.2 in clinical trials.
  • To highlight the progress and potential of CLDN-targeted therapies, particularly for gastric cancer.

Main Methods:

  • Review of clinical trial data for CLDN-targeting agents.
  • Analysis of efficacy metrics such as objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Main Results:

  • CLDN18.2-targeted therapies are most advanced, with zolbetuximab showing a 9% ORR and improving survival with chemotherapy.
  • Other CLDN18.2-targeting agents (osemitamab, ADCs AZD0901, IBI343, LM-302) achieved 28-60% ORRs in Phase III trials.
  • Bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells targeting CLDN4, CLDN6, or CLDN18.2 are in earlier clinical phases.

Conclusions:

  • CLDN-targeted therapies, especially for CLDN18.2, represent a promising new avenue in cancer treatment.
  • Several CLDN-targeting drugs have received fast track or priority review designations, indicating significant therapeutic potential.
Keywords:
TGF‑βWNTepithelial‑mesenchymal transitionfibroblast growth factor receptorimmunosuppressive tumor microenvironmentintratumor heterogeneitynon‑small cell lung cancerovarian cancerpancreatic cancersplicing variant

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