Universität zu Köln

Hartmann, Milan JM (2026). Emerging therapy options for gastric adenocarcinoma - a comprehensive review and analysis of clinical trials. PhD thesis, Universität zu Köln.

PDF (Manuscript) Doktorarbeit Milan Hartmann - Emerging therapy options for gastric adenocarcinoma June 2026 revised.pdf - Published Version Download (3MB)

Abstract

Gastric adenocarcinoma continues to be a significant global health burden and ranking among the top five leading causes of cancer-related mortality. Although there have been advancements in surgical and chemotherapeutic strategies, the prognosis for advanced and metastatic stages is still poor, stressing the urgency for more effective and personalized treatment options. This thesis explored the landscape of targeted therapies that are currently under investigation for the treatment of gastric adenocarcinoma, with the focus on active and completed clinical trials to comprehend new arising options for treatment. We utilized databases such as ClinicalTrials.gov, DrugBank, KEGG, and PubMed, and provided a comprehensive analysis to identify the range of molecular targets, therapeutic classes, and biological pathways involved. The study reviewed the already approved therapies and distinguished 2433 clinical trials investigating 905 investigational agents targeting 320 distinct molecular pathways or gene products. Among the most promising targets under investigation are CLDN18.2, FGFR2b, MET, and immune checkpoint combinations, alongside antibody-drug conjugates and bispecific antibodies. The thesis further integrated genomic and signaling pathway analysis using data from KEGG and TCGA, highlighting frequently altered pathways such as PI3K/Akt, RTK-RAS, p53, TGF-β, and Wnt/β-catenin. A network analysis of target gene interactions underscores the necessity of multi-targeted and biomarker-enriched strategies as well as further research to deepen the understanding molecular composition of gastric cancer. While overall there are several promising trials and agents, the current therapeutic pipeline faces various challenges, especially limited biomarker availability, variability in treatment response across patient populations, and a general need for more extensive inclusion criteria in clinical trials. This means we need to further deepen our understanding of molecular profiling, adaptive trial designs, and personalize treatment approaches. In conclusion, the field of targeted therapy for gastric cancer is still rapidly evolving. With continued innovation and a shift toward biomarker-guided treatment, there is hope to significantly improve patient outcomes and transition from generalized treatment paradigms to precision oncology as in most of the other carcinoma. This work provides a structured overview of ongoing developments and contributes to the growing body of knowledge essential for advancing gastric cancer therapy.