Translating Gastric Cancer Genomics into Targeted Therapy: Mechanistic Insights from Animal Models and...

Area of Science:

• Oncology
• Genetics
• Translational Medicine

Background:

• Gastric cancer is a major global health issue with significant molecular diversity.
• Genomic profiling reveals key oncogenes, tumor suppressors, and pathway regulators in gastric cancer.
• Existing preclinical models have limitations in predicting clinical efficacy of targeted therapies.

Purpose of the Study:

• To systematically review gastric cancer-associated genes and their biological functions.
• To summarize and evaluate animal models used in gastric cancer research.
• To critically analyze clinical translation successes and failures of targeted therapies.

Main Methods:

• Categorization of gastric cancer genes by biological function.
• Review of representative animal models for gastric cancer.
• Critical examination of clinical trial outcomes for targeted therapies.

Main Results:

• Identified key genes like HER2, PIK3CA, TP53, and CDH1 in gastric cancer.
• Highlighted translational challenges where therapies effective in models failed in patients.
• Noted success of HER2- and CLDN18.2-targeted therapies due to specific dependencies and patient selection.

Conclusions:

• Biologically faithful preclinical models are crucial for successful gastric cancer drug development.
• Precision-driven strategies, including biomarker-based patient selection, are essential for clinical translation.
• Understanding molecular heterogeneity is key to overcoming translational barriers in gastric cancer therapy.