Advanced biliary tract cancer represents one of the most challenging gastrointestinal malignancies in China, with increasing incidence and extremely poor prognosis due to late-stage diagnosis and limited treatment options. The integration of precision medicine approaches has transformed the therapeutic landscape by enabling personalized treatment strategies based on molecular profiling, tumor characteristics, and patient-specific factors. Recent developments encompass novel chemotherapy combinations, targeted therapies for specific genetic alterations, immunotherapy approaches, and emerging biomarkers that guide treatment selection and predict therapeutic responses.
Traditional gemcitabine plus cisplatin regimens have served as the backbone of first-line treatment, but innovative combinations incorporating albumin-bound paclitaxel, S-1, or modified FOLFIRINOX have demonstrated improved efficacy in Chinese patient populations. Phase II trials comparing albumin-paclitaxel plus cisplatin versus gemcitabine plus cisplatin showed promising response rates, while nab-paclitaxel combined with S-1 achieved encouraging survival outcomes. The integration of hepatic arterial infusion chemotherapy with systemic regimens has emerged as a particularly effective approach for intrahepatic cholangiocarcinoma, leveraging regional drug delivery to maximize tumor exposure while minimizing systemic toxicity.
The molecular landscape of biliary tract cancer in China exhibits distinct characteristics compared to Western populations, with unique genetic signatures influencing treatment decisions. Comprehensive genomic profiling has revealed actionable targets including IDH1/2 mutations, FGFR2 fusions, and HER2 amplifications, enabling precision targeting with specific inhibitors. The high prevalence of Epstein-Barr virus-associated cases in Asian populations presents both challenges and opportunities for targeted interventions. Somatic genetic aberrations differ significantly between Chinese and US patients, emphasizing the importance of population-specific molecular databases for optimal therapeutic selection.
Immunotherapy has revolutionized treatment paradigms through immune checkpoint inhibitors, particularly when combined with chemotherapy or targeted agents. PD-1 inhibitors including camrelizumab, sintilimab, and tislelizumab have demonstrated substantial efficacy in Chinese trials, with combination approaches showing superior outcomes compared to monotherapy. The TOPAZ-1 study established durvalumab plus gemcitabine and cisplatin as a new standard of care, achieving median overall survival of 12.8 months compared to 11.5 months with chemotherapy alone. Innovative triple combinations incorporating PD-1 inhibitors, lenvatinib, and chemotherapy have achieved remarkable response rates exceeding 80% in potentially resectable cases, opening new avenues for conversion therapy.
Targeted therapy approaches have shown particular promise for specific molecular subtypes. FGFR inhibitors represent breakthrough treatments for FGFR2 fusion-positive cholangiocarcinoma, while IDH inhibitors target mutant IDH1/2 tumors. HER2-directed therapies including trastuzumab and pertuzumab combinations have demonstrated efficacy in HER2-amplified cases, with response rates significantly higher than conventional chemotherapy. The development of novel agents targeting less common alterations continues to expand therapeutic options for molecularly selected patient populations.
Biomarker development has become crucial for treatment optimization, with circulating tumor DNA, EBV DNA levels, and specific genetic alterations serving as predictive indicators. The integration of liquid biopsy approaches enables real-time monitoring of treatment response and early detection of resistance mechanisms. Peripheral blood-based biomarkers including neutrophil-to-lymphocyte ratios and circulating cytokine profiles provide additional prognostic information. Radiomics features from baseline imaging studies offer non-invasive assessment of tumor characteristics that may predict therapeutic sensitivity.
Challenges remain in implementing precision medicine approaches across diverse clinical settings in China. Regional variations in molecular testing capabilities, treatment accessibility, and healthcare infrastructure create disparities in precision oncology implementation. The high cost of targeted therapies and molecular profiling limits widespread adoption, particularly in resource-limited settings. Standardization of biomarker assays and establishment of national databases are essential for optimizing patient care and advancing research initiatives.
Future directions emphasize the development of novel combination strategies that integrate multiple precision medicine modalities. The incorporation of artificial intelligence and machine learning approaches may enhance biomarker discovery and treatment selection algorithms. Expansion of clinical trial networks across China will facilitate validation of precision medicine approaches in diverse patient populations. Integration of traditional Chinese medicine principles with modern precision oncology represents a unique opportunity for developing innovative therapeutic strategies. Continued investment in molecular profiling infrastructure and healthcare professional education will be essential for realizing the full potential of precision medicine in advanced biliary tract cancer treatment across China..

DOI
10.1007/s11684-025-1144-4