Exploring in vitro modeling in hepatocarcinogenesis research: morphological and molecular features and similarities to the corresponding human disease

Author(s)

Valente, Leticia Cardoso ; Bacil, Gabriel Prata ; Riechelmann-Casarin, Luana ; Barbosa, Giullia Cavichiolli ; Barbisan, Luis Fernando ; Romualdo, Guilherme Ribeiro

• Document type: Journal article
• Source: Life Sciences; v. 351, p. 13-pg., 2024-06-13.

Abstract

The hepatocellular carcinoma (HCC) features a remarkable epidemiological burden, ranking as the third most lethal cancer worldwide. As the HCC-related molecular and cellular complexity unfolds as the disease progresses, the use of a myriad of in vitro models available is mandatory in translational preclinical research setups. In this review paper, we will compile cutting-edge information on the in vitro bioassays for HCC research, (A) emphasizing their morphological and molecular parallels with human HCC; (B) delineating the advantages and limitations of their application; and (C) offering perspectives on their prospective applications. While bidimensional (2D) (co) culture setups provide a rapid low-cost strategy for metabolism and drug screening investigations, tridimensional (3D) (co) culture bioassays - including patient-derived protocols as organoids and precision cut slices - surpass some of the 2D strategies limitations, mimicking the complex microarchitecture and cellular and non-cellular microenvironment observed in human HCC. 3D models have become invaluable tools to unveil HCC pathophysiology and targeted therapy. In both setups, the recapitulation of HCC in different etiologies/backgrounds (i.e., viral, fibrosis, and fatty liver) may be considered as a fundamental guide for obtaining translational findings. Therefore, a "multimodel" approach - encompassing the advantages of different in vitro bioassays - is encouraged to circumvent "model-biased" outcomes in preclinical HCC research. (AU)

• FAPESP's process: 22/13402-9 - Effects of carboxymethylcellulose and polysorbate 80 food additive on hepatocarcinogenesis-associated non-alcoholic fatty liver disease.
• Grantee: Gabriel Bacil Prata
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 23/05411-0 - Effects of the combination of coffee compounds and antitumor agents on Hepatocellular Carcinoma: in vitro and in vivo investigation
• Grantee: Leticia Cardoso Valente
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 23/08751-7 - Multimodel Drug Screening Platform (MDSP): preclinical and molecular insights for colon and liver cancer management
• Grantee: Guilherme Ribeiro Romualdo
• Support Opportunities: Scholarships in Brazil - Generation Project
• FAPESP's process: 22/16633-1 - Effects of Carboxymethylcellulose and Polysorbate 80 food additive on Nonalcoholic Fatty Liver Disease-associated hepatocarcinogenesis
• Grantee: Luís Fernando Barbisan
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/17585-3 - Does Caffeic Acid Enhance the Antitumoral Response of Sorafenib on Hepatocellular Carcinoma? An In Vitro Approach.
• Grantee: Luana Riechelmann Casarin
• Support Opportunities: Scholarships in Brazil - Scientific Initiation