yemenjmedYemen Journal of MedicinecoVolume 5 Issue 2MultidisciplinaryEnglishMay-August 2026NNY20260826ArticleCholangiocarcinoma in 2026: Pathophysiology, Diagnostic Advances, and Evolving Therapeutic Landscape—A Narrative ReviewEnglishY355364ElmukhtarHabas1EnglishNAmlHabas2EnglishYAmnna AliRayani3EnglishYAlaHabas4EnglishYEshrakHabas5EnglishY10.63475/yjm.v5i2.0472Cholangiocarcinoma (CCA) is a heterogeneous malignancy of the biliary epithelium, classified into intrahepatic, perihilar, and distal subtypes with distinct molecular signatures, risk factor profiles, and clinical behavior. This narrative review synthesizes current understanding of CCA pathophysiology, established and emerging risk factors, clinical presentation, diagnostic modalities, persistent gaps in diagnosis and treatment, and recent therapeutic advances through mid-2026. Molecular classification has matured substantially, with fibroblast growth factor receptor 2 (FGFR2) fusions and isocitrate dehydrogenase 1 (IDH1) mutations enriched in intrahepatic disease and human epidermal growth factor receptor 2 (HER2) amplification more common in extrahepatic subtypes, each now targetable with U.S. Food and Drug Administration (FDA)-approved agents, including pemigatinib, futibatinib, ivosidenib, and zanidatamab. First- line systemic therapy has shifted meaningfully with the incorporation of immune checkpoint inhibition, established through the TOPAZ-1 and KEYNOTE-966 trials, and investigational first- line FGFR2 inhibition data from the FIGHT-302 trial presented in 2026. Despite these advances, diagnostic delay remains common, driven by the nonspecific presentation of intrahepatic disease and technical limitations in tissue confirmation and serum biomarkers. A distinct and underexplored gap concerns the epidemiology, diagnostic access, and treatment availability for CCA across Arab and African populations, where regional incidence data, molecular testing infrastructure, and equitable access to newly approved therapies remain limited. This review argues that translating molecular and therapeutic precision into equitable outcomes across all affected populations remains the central unmet task facing the field.EnglishCholangiocarcinoma, bile duct neoplasms, FGFR2, IDH1, immunotherapy, health equityhttps://www.yemenjmed.com/admin/abstract?id=451References1619