Emerging evidence of targeting non-oncogenic drivers for gastric cancer: Claudin18.2 and beyond

Area of Science:

• Oncology
• Molecular Biology
• Drug Development

Background:

• Human epidermal growth factor receptor 2 (HER2) was the first successful molecular target in gastric cancer therapy.
• Emerging evidence highlights Claudin18.2 (CLDN18.2) as a significant therapeutic target, shifting focus beyond conventional oncogenic drivers.
• Therapeutic strategies are expanding to include tumor-associated molecules not critical for tumor growth, such as trophoblast cell surface antigen 2, Caprin-1, and Nectin-4.

Purpose of the Study:

• To provide an update on Claudin18.2 (CLDN18.2)-directed therapies for gastric cancer.
• To explore novel therapeutic strategies targeting non-oncogenic drivers in advanced gastric cancer.
• To discuss challenges and future directions for next-generation molecular targeted therapy in gastric cancer.

Main Methods:

• Review of current literature on CLDN18.2-directed therapies.
• Exploration of innovative therapeutic approaches including antibody-drug conjugates, bispecific antibodies, and CAR T-cell therapy.
• Analysis of emerging non-oncogenic targets for gastric cancer treatment.

Main Results:

• Claudin18.2 (CLDN18.2) has emerged as a promising target, reshaping the therapeutic landscape for gastric cancer.
• Innovative approaches like antibody-drug conjugates and CAR T-cell therapy show potential for targeting tissue-associated antigens.
• Non-oncogenic targets offer new avenues for treating advanced gastric cancer.

Conclusions:

• Claudin18.2 (CLDN18.2) and other non-oncogenic targets represent a paradigm shift in gastric cancer therapy.
• Advanced therapeutic modalities are accelerating the development of targeted treatments.
• Addressing challenges like biomarker overlap and resistance is crucial for future progress in molecular targeted therapy.