Precision targeting of CLDN18.2: A new therapeutic paradigm for gastric cancer

Area of Science:

• Oncology
• Immunotherapy
• Gastroenterology

Background:

• Claudin 18.2 (CLDN18.2) is a promising therapeutic target in gastric cancer (GC).
• Zolbetuximab, a CLDN18.2-targeted monoclonal antibody (mAb), is approved for HER2-negative, CLDN18.2-positive gastric adenocarcinoma.
• This review focuses on CLDN18.2-targeted therapies and their clinical development.

Purpose of the Study:

• To summarize current advances in CLDN18.2-targeted therapies for GC.
• To highlight the clinical development of mAbs, including zolbetuximab and next-generation antibodies.
• To review emerging strategies like antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and CAR-T cell therapy.

Main Methods:

• Literature review of CLDN18.2-targeted therapies in GC.
• Focus on clinical development of monoclonal antibodies (mAbs).
• Summary of antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and CAR-T cell therapy.

Main Results:

• Zolbetuximab is an approved first-line treatment for specific GC patients.
• Emerging next-generation antibodies and combination strategies are under development.
• ADCs, BsAbs, and CAR-T cell therapies show potential in CLDN18.2-targeted treatment.

Conclusions:

• Precision targeting of CLDN18.2 is a promising approach for GC therapy.
• Biomarker-guided strategies are replacing conventional chemotherapy.
• Further development of novel agents and combination therapies may improve patient outcomes.