Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Blidisel, Alexandru; Marcovici, Iasmina; Coricovac, Dorina; Hut, Florin; Dehelean, Cristina Adriana; Cretu, Octavian Marius

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is characterized by a broad molecular and genetic heterogeneity, which makes it a challenging subject in terms of the underlying mechanisms, response and resistance to treatment, and finding novel therapeutic options. Nowadays, new experimental models (3D in vitro models, in vivo mouse and non-mouse models, and computational studies) allow more detailed studies of hepatocellular carcinoma pathogenesis and treatment. Here, we provide insights into the current preclinical models frequently applied for the study of hepatocellular carcinoma. ABSTRACT: Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.