- To outline the limitations/shortcomings of currently available animal models of liver cancer.
- To describe the rationale, genetic basis, and lab methods for development of the Oncopig cancer model (OCM) as a novel animal model for hepatocellular carcinoma (HCC).
- To recognize the potential opportunities for future preclinical application of the OCM in Interventional Radiology (IR) translational research.
Animal models play a critical role in advancing cancer research for application to clinical care. IRs have employed many different models to investigate HCC, but to date, there have been significant limitations with existing systems. The large size of the pig and its similarity to humans in anatomy, physiology, metabolism, and genetics make it an ideal platform to develop a genetically defined, large animal cancer model. This exhibit describes the development of the OCM as a biologically analogous and clinically relevant model for human HCC to be used to improve detection, treatment, and follow-up of liver tumors treated via IR locoregional therapies (LRTs).
Clinical Findings/Procedure Details:
The Oncopig is a transgenic pig that develops site/cell specific tumors following adenovirus mediated Cre recombinase (AdCre) exposure. As an HCC model, the OCM was designed to manifest those mutations most commonly found in >50% of human cancers, namely P53(R167H) (a defining HCC oncogenesis event) and KRAS(G12D). For tumor development, hepatocytes from Oncopig livers are procured, isolated, and then treated in vitro with Cre. Transformed cells proliferate, and upon phenotyping, express hepatocyte specific marker genes (albumin, HNF4, G6P, and oncogenic TP53 and Kras). OCM HCC lines form tumors within 2 weeks of injection into immune compromised mice, and current studies aim to autologously administer transformed cells into OCM host liver for HCC development.
Conclusion and/or Teaching Points:
The OCM provides a realistic human HCC model that overcomes deficiencies of current animal models. Given its similarity to humans in both biology and size, the OCM allows for translational LRT studies that could not be performed in humans, and thus represents a new paradigm to investigate HCC from an innovative and clinically relevant perspective.