Recent advances in molecular classification and multimodal treatment of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and is characterized by aggressive biological behavior and poor prognosis. Surgical resection remains the only potentially curative treatment; however, most patients are ineligible for surgery at diagnosis, and recurrence rates remain high even after curative resection.In recent years, locoregional therapies including transarterial chemoembolization, hepatic arterial infusion chemotherapy, and radiotherapy have achieved promising clinical outcomes and are increasingly incorporated into multimodal treatment strategies alongside surgery and systemic therapy. Liver transplantation has also shown potential benefits in carefully selected early-stage cases. Meanwhile, advances in targeted therapy and immunotherapy—including phase III trials of gemcitabine–cisplatin combined with PD‑1/PD‑L1 inhibitors—have further supported the development of personalized, multidisciplinary treatment strategies in advanced disease.The rapid development of genomic sequencing and tumor microenvironment research has enabled molecular classification of ICC, providing valuable guidance for the selection of targeted and immune-based therapies. Importantly, molecular profiling is now also influencing patient selection for resection and transplantation within multimodal treatment pathways, and recent data support fluoropyrimidine-based adjuvant therapy and emerging perioperative chemotherapy strategies in resectable biliary tract cancers. Nevertheless, certain treatment strategies, particularly in the context of multimodal integration, require further validation through large-scale prospective clinical studies.This review summarizes recent progress in molecular classification, local and systemic therapeutic approaches, and highlights how molecular profiling and biomarker-guided strategies contribute to personalized, precision, and multimodal treatment of intrahepatic cholangiocarcinoma.