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Targeting claudins in cancer

Yuki Niwa1, Shunsuke Matsushita1, Izuma Nakayama2

  • 1Graduate School of Pharmaceutical Sciences, The University of Osaka, Suita, Osaka, Japan.

Nature Reviews. Drug Discovery
|May 28, 2026
PubMed

Insights

Claudins are key regulators of epithelial function and tight junctions. Targeting claudins, like CLDN-18.2 with zolbetuximab for gastric cancer, offers promising new avenues for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Epithelial-derived malignancies represent the majority of human tumors, posing significant treatment challenges due to heterogeneity, metastasis, and therapy resistance.
  • Claudins, a family of tetra-transmembrane proteins, are crucial regulators of epithelial function and integral components of tight junctions, controlling barrier integrity and cellular organization.

Purpose of the Study:

  • To review the evolving landscape of claudin-targeting therapeutics in cancer treatment.
  • To examine key advances, emerging challenges, and future prospects in exploiting claudins as therapeutic targets.

Main Methods:

  • Review of scientific literature focusing on claudin family proteins in epithelial biology and cancer.
  • Analysis of clinical studies and therapeutic developments targeting claudins, including antibody-based therapies.

Main Results:

  • Claudin expression is frequently dysregulated in various cancers, indicating their potential as therapeutic targets.
  • The development of zolbetuximab, a CLDN-18.2-targeted antibody, represents a significant advancement, recently approved for gastric cancer treatment.
  • Targeting claudins holds promise for expanding treatment options for various cancers.

Conclusions:

  • Claudin-targeting therapeutics represent a promising frontier in oncology.
  • The success of zolbetuximab highlights the therapeutic potential of targeting specific claudins.
  • Continued research into claudin biology and targeted therapies is crucial for advancing cancer treatment strategies.

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