Combined hepatocellular cholangiocarcinoma (cHCC-CC): an update of genetics, molecular biology, and therapeutic interventions Chara Stavraka,1,* Hannah Rush,1,* Paul Ross1,2 1Department of Medical Oncology, Guy’s Cancer, Guy’s & St Thomas’ NHS Foundation Trust, London, UK; 2Department of Oncology, King’s College Hospital NHS Foundation Trust, London, UK *These authors contributed equally to this work Abstract: Combined hepatocellular cholangiocarcinoma (CC) is a rare and aggressive primary hepatic malignancy with significant histological and biological heterogeneity. It presents with more aggressive behavior and worse survival outcomes than either hepatocellular carcinoma or CC and remains a diagnostic challenge. An accurate diagnosis is crucial for its optimal management. Major hepatectomy with hilar node resection remains the mainstay of treatment in operable cases. Advances in the genetic and molecular characterization of this tumor will contribute to the better understanding of its pathogenesis and shape its future management. Keywords: cholangiocarcinoma, hepatocellular carcinoma, combined, genetics, molecular biology, treatment, mixed liver tumors, primary liver cancer