Identification and prioritization of high-frequency biomarkers and therapeutic targets in gastric cancer trials.

BACKGROUND

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. An investigation of clinical trials and therapeutic targets for GC was conducted.

METHODS

Using the Trialtrove database, we anlyzed global and Chinese clinical trials on GC. Subsequently, we investigated oxaliplatin, S-1, apatinib, nivolumab, and sintilimab, alongside associated oncogenic biomarkers and therapeutic targets. The safety of these targets was evaluated through a joint analysis of the GTEx-RNA, HPA-RNA, and HPA-Proteins datasets. Finally, we assessed their specificity and clinical prospects using HPA pathology and CPTAC data.

RESULTS

Currently, global clinical trials on GC are primarily concentrated in China (> 50%) and the United States. Since the survival benefit of HER2-positive GC targeted therapy was first confirmed in 2010. Trastuzumab received FDA approval, targeted and immunotherapies have played a pivotal role in both monotherapy and combination treatment of GC. Nivolumab, Trastuzumab, and China-developed anticancer agents such as apatinib and sintilimab are now being used in combination with traditional chemotherapeutic drugs like oxaliplatin and S-1 for GC treatment. At present, only PD-1, VEGFR2, and HER2 are approved GC therapeutic targets. Our analysis indicates that most potential targets exhibit poor safety and low specificity. However, FGFR2, CTLA4, and TROP demonstrate favorable safety and specificity profiles, suggesting promising potential for GC targeted therapy and prognostic monitoring.

CONCLUSIONS

By analyzing the clinical trial landscape and the safety and specificity of therapeutic targets for GC, this study offers a reference for future clinical investigation.