Models of intrahepatic cholangiocarcinoma: novel tools and therapeutic applications

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy, and a number of recent studies have identified an increasing trend in incidence and mortality. As an aggressive disease characterized by early metastasis, surgical resection is not an option for most patients, and chemotherapy has limited benefit. Thus, the prognosis is extremely poor, warranting the development of novel models to improve detection and treatment strategies for this lethal cancer. In this regard, significant technological advancements have provided key tools to model and study iCCA. Furthermore, these technologies are addressing the need for models that can readily be adapted to address different genetic contexts, an important consideration for genetically diverse cancers such as iCCA. In this review, we outline these various available tools, discussing specifically how they have been employed to study iCCA while highlighting important therapeutic implications. Finally, we discuss novel strategies utilizing patient-derived tumor tissue which have promising translational applications.