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Innovative CAR-T approaches targeting Claudin 18.2 to counteract drug resistance in gastric cancer

Giovanni Calice1, Carlo Calabrese1, Tiziana Notarangelo1

  • 1IRCCS CROB Centro di Riferimento Oncologico della Basilicata, PZ, Rionero in Vulture, Italy.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|December 3, 2025
PubMed

Insights

Claudin18.2, a protein in gastric tumors, drives drug resistance and poor outcomes by affecting cell survival pathways. Targeting Claudin18.2 shows promise for new gastric cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Claudins are integral tight junction proteins.
  • Aberrant Claudin18.2 expression is observed in gastric tumors.
  • Claudin18.2 disrupts epithelial integrity and promotes tumor progression.

Purpose of the Study:

  • To investigate the role of Claudin18.2 in gastric cancer drug resistance.
  • To explore Claudin18.2 as a potential therapeutic target and biomarker.

Main Methods:

  • Analysis of cell death and survival pathways (apoptosis, autophagy, epithelial-mesenchymal transition).
  • Investigation of crosstalk with efflux transporters and pro-survival signaling.
  • Review of clinical trial data for Claudin18.2-targeted therapies.

Main Results:

  • Claudin18.2 enhances multidrug resistance and is linked to adverse clinical outcomes.
  • Claudin18.2 reinforces chemoresistance to platinum-based drugs and fluoropyrimidines.
  • Claudin18.2 is identified as a biomarker for aggressive gastric disease.

Conclusions:

  • Claudin18.2 plays a critical role in gastric cancer progression and therapeutic failure.
  • Claudin18.2 represents a promising therapeutic target for gastric cancer.
  • Monoclonal antibodies and antibody-drug conjugates targeting Claudin18.2 demonstrate encouraging antitumor activity in clinical trials.
Keywords:
ChemoresistanceClaudinGastric cancerTarget therapyTumor microenvironment

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