The importance of preclinical models for cholangiocarcinoma drug discovery.

Abstract

Introduction: Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- and extrahepatic biliary system (intrahepatic and extrahepatic cholangiocarcinoma) and gallbladder cancer with the common feature of a poor prognosis, despite increasing molecular knowledge of associated genetic aberrations and possible targeted therapies. Therefore, the search for even more precise and individualized therapies is ongoing and preclinical tumor models are central to the development of such new approaches.

Areas covered: The models described in the current review include simple and advanced in vitro and in vivo models, including cell lines, 2D monolayer, spheroid and organoid cultures, 3D bioprinting, patient-derived xenografts, and more recently, machine-perfusion platform-based models of resected liver specimens. All these models have individual advantages, disadvantages and limitations that need to be considered depending on the desired application.

Expert opinion: In addition to potential cost limitations, availability of BTC cell types, time required for model establishment and growth success rate, the individual models differently reflect relevant characteristics such as tumor heterogeneity, spatial tumor-stroma microenvironment interactions, metabolic and nutritional gradients and immunological interactions. Therefore, a consequent combination of different models may be required to improve clinical study outcomes by strengthening the preclinical data basis.