Precision targeting in biliary tract cancer therapy: A geographical, target, and efficacy analysis of clinical trials

Despite a significant increase in clinical trials for biliary tract cancers (BTCs) over the past decade, progress in precision therapy has been limited by insufficient understanding of treatment strategies and target specificity.

Based on 873 clinical trials for BTCs from the Informa database, we conducted an analysis of the geographical distribution, research phase, treatment modalities, and target characteristics for BTCs over the past decade. We further integrated transcriptomic and proteomic data from the Human Protein Atlas (HPA) to evaluate the differential expression of targets in normal and tumor tissues. The specificity and potential of targets were further analyzed.

Clinical trials for BTCs exhibited region-specific dominance, with China and the United States accounting for 35% and 32.5% of trials, respectively. Current major breakthroughs in clinical trials involve combination therapies. Globally, chemotherapy combined with targeted therapy is predominant, whereas China primarily focuses on chemotherapy combined with immunotherapy. Hepatic arterial infusion chemotherapy (HAIC) combined with targeted/immunotherapy represents a distinctive treatment strategy in China. Innovative therapies, such as antibody-drug conjugates (ADCs) and cancer vaccines, are primarily in Phase I/II. The VEGF pathway, FGFR fusions, and HER2 amplification have garnered significant attention for clinical translation. CHEK1, ATR, DNMT1, AURKA, and CA9 represent potential targets demonstrating high safety and specificity.

This study provides a comprehensive analysis of the clinical trial landscape for BTCs and evaluates the safety and specificity of therapeutic targets, serving as a reference for future BTC research.