Genetic and molecular advancements in combined hepatocellular-cholangiocarcinoma: Addressing a persistent clinical conundrum

Abstract

Owing to the heterogeneous histomorphology and variable proportion presentation of cholangiocarcinoma (CCa) and hepatocellular carcinoma (HCC), accurate diagnosis and treatment of combined or mixed hepatocellular cholangiocarcinoma (CHC) remains a critical conundrum (Chu et al., 2024). The rare hepatic neoplasm accounts for < 5 % of all primary hepatic neoplasms with insufficiently complex pre-operative diagnostic data. Liver-directed approaches such as hepatic arterial infusion chemotherapy, radioembolization, transarterial chemoembolization and ablative therapies fail to achieve adequate efficacy due to the overlapping biological and clinical patterns between its cancerous ingredients. The accuracy of alpha fetoprotein (AFP), CA 19-9 biomarkers as well as cross-sectional imaging for pre-operative diagnosis is hindered by the biphenotypic nature of the disease. Gemcitabine and cisplatin constitute the current first line treatment; survival remains dismal, highlighting the urgent need for comprehensive genetic and molecular profiling (