Recent advances in targeted and immunotherapeutic strategies for cholangiocarcinoma: A comprehensive review

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy originating from biliary epithelial cells. Due to challenges in early diagnosis and the limited efficacy of traditional treatments, the prognosis for patients remains poor. Recent advances in molecular profiling and immunology have significantly altered the therapeutic landscape of CCA. Genomic studies have shown that approximately 40% of CCA cases carry targetable driver mutations, including FGFR2 fusions and IDH1/2 mutations. Targeted therapies directed at these alterations have notably improved survival outcomes in patients with specific molecular subtypes. Additionally, immunotherapies targeting the immunosuppressive tumor microenvironment (TME) of CCA have made substantial progress. The combination of immune checkpoint inhibitors (ICIs) with chemotherapy has become the new standard first-line treatment, and emerging strategies involving dual immunotherapy, ICIs with targeted therapies, and ICIs with local-regional treatments have demonstrated promising synergy. Nevertheless, challenges such as resistance to targeted therapies, barriers posed by the immunosuppressive TME, and the absence of universal biomarkers continue to pose significant obstacles.