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Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials

Daisuke Kyuno1,2, Akira Takasawa1, Kumi Takasawa1

  • 1Department of Pathology, Sapporo Medical University, Sapporo, Japan.

Tissue Barriers
|September 6, 2021
PubMed

Insights

Claudin-18.2 is overexpressed in cancers and is a promising therapeutic target. Zolbetuximab, a claudin-18.2 antibody, shows positive results in clinical trials for advanced cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Claudins are key tight junction proteins regulating cell adhesion and polarity.
  • Aberrant claudin expression, particularly claudin-18.2 overexpression, is implicated in carcinogenesis.
  • Claudin-18.2 is a validated therapeutic target in several cancer types.

Purpose of the Study:

  • To review the role of claudin-18.2 in cancer research.
  • To discuss the clinical applications of targeting claudin-18.2.
  • To highlight claudin-18.2 as a potential therapeutic strategy for advanced cancers.

Main Methods:

  • Literature review of basic cancer research on claudin-18.2.
  • Analysis of clinical trial data for claudin-18.2-targeted therapies.
  • Synthesis of current insights into claudin-18.2's function and therapeutic potential.

Main Results:

  • Claudin-18.2 is upregulated and mislocalized in various cancers, driving carcinogenesis.
  • Zolbetuximab, a monoclonal antibody targeting claudin-18.2, demonstrated positive clinical trial outcomes.
  • The antibody treatment showed a favorable safety profile with few high-grade adverse events.

Conclusions:

  • Claudin-18.2 is a significant target for novel cancer therapeutics.
  • Targeting claudin-18.2 with agents like zolbetuximab offers a promising treatment avenue.
  • Further understanding of claudin-18.2 will advance treatment strategies for patients with poor prognoses.
Keywords:
Tight junctioncancerclaudin-18.2zolbetuximab

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