Abstract
The current landscape of second-line treatment for cholangiocarcinoma (CCA) appears to be evolving, with emerging strategies offering potential improvements over traditional approaches. Although conventional chemotherapy demonstrates limited efficacy following progression after first-line therapy, the development of targeted therapies and immunotherapies is creating new possibilities for enhancing clinical outcomes. The increasing focus on molecular biomarkers-such as isocitrate dehydrogenase (IDH), B-raf kinase (BRAF), and neurotrophic receptor tyrosine kinase (NTRK) mutations, as well as fibroblast growth factor receptor (FGFR2) fusions and HER2/neu overexpression-represents a significant advancement in enabling precise, targeted treatment options. Evidence from recently completed and ongoing clinical trials evaluating these therapies, both as monotherapy and in combination with chemotherapy and/or immunotherapy, supports this shift. Continued research aimed at refining treatment selection and advancing personalized therapeutic strategies is essential, with the goal of achieving longer survival and improved quality of life for patients undergoing second-line therapy for CCA.