Oncopig fulfills the unmet clinical modeling needs for hepatocellular carcinoma

Volume 11, Issue 28 of Oncotarget features "Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation" by Gaba et, al. which reported that reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs.

Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug-metabolizing enzyme expression.

The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous injection into immunodeficient mice and Oncopigs.

Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers.

Finally, Oncopig HCC cells are amenable to gene editing for the development of personalized HCC tumors.

Dr. Kyle M. Schachtschneider from The Department of Radiology and The Biological Resources Laboratory at The University of Illinois at Chicago as well as The National Center for Supercomputing Application at The University of Illinois at Urbana-Champaign said,

Hepatocellular carcinoma (HCC)–the most common type of primary liver cancer–is an aggressive cancer that spans more than 850,000 new yearly diagnoses and causes 800,000 annual deaths, representing the fifth most common cancer globally and the second most common cause of cancer-related death worldwide."

Dr. Kyle M. Schachtschneider, Department of Radiology and Biological Resources Laboratory, The University of Illinois

The rabbit VX2 model has been considered the most relevant and widely used model to test HCC LRTs to date.

As such, there is a crucial need for more clinically relevant large animal models that faithfully recapitulate human HCC to address unmet clinical needs and serve as a bridge between murine studies and clinical practice.

This study describes the utilization of the Oncopig Cancer Model for the development of a clinically relevant, translational porcine HCC model.

The Oncopig Cancer Model is a transgenic pig model that develops site and cell-specific tumors following Cre recombinase induced expression of heterozygous KRASG12D and TP53R167H transgenes.

The large size of the pig and its similarities with humans in terms of anatomy, physiology, metabolism, immunity, and genetics make it an ideal model species for the development of a large animal cancer model.

Development of Oncopig HCC cell lines has been previously described, however, prior work was limited to characterization of HCC cell lines derived from three Oncopigs, minimal in vitro and in vivo profiling, and no description of intrahepatic tumors.

As such, this study was undertaken to test the hypothesis that phenotypically consistent Oncopig HCC cells that faithfully recapitulate the in vitro features of human HCC can be developed across a large Oncopig cohort and that these cells can be utilized to develop clinically relevant intrahepatic HCC tumors in Oncopigs.

The Schachtschneider Research Team concluded in their Oncotarget Research Paper, "the Oncopig HCC model offers a novel, physiologically and anatomically relevant cancer model for which a multitude of innovative therapeutic modalities can be applied and tested while significantly reducing the costs, confounding variables seen in human subjects, and lengthy conduct of human clinical trials. Importantly, the Oncopig can be utilized to conduct correlative studies for more efficient and consistent investigation of new therapies. Its size allows for utilization of the same methods and instruments used in human clinical practice, including CT and magnetic resonance imaging technologies. This model is thus amenable to developing and establishing medical imaging standards related to diagnosing HCC tumors and tracking treatment response using accepted radiologic criteria, a critical facet of therapeutic discovery and validation. Importantly, the Oncopig is also immunocompetent, lending itself to investigation of immunotherapies  Therefore, the Oncopig fulfills the currently unmet clinical modeling needs for HCC, particularly for pilot investigations of experimental therapies or experimental therapeutic combinations not feasible in human subjects."

Journal reference:

Gaba, R. C., et al. (2020) Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation. Oncotarget. doi.org/10.18632/oncotarget.27647.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
Post a new comment
Azthena logo

AZoM.com powered by Azthena AI

Your AI Assistant finding answers from trusted AZoM content

Your AI Powered Scientific Assistant

Hi, I'm Azthena, you can trust me to find commercial scientific answers from AZoNetwork.com.

A few things you need to know before we start. Please read and accept to continue.

  • Use of “Azthena” is subject to the terms and conditions of use as set out by OpenAI.
  • Content provided on any AZoNetwork sites are subject to the site Terms & Conditions and Privacy Policy.
  • Large Language Models can make mistakes. Consider checking important information.

Great. Ask your question.

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Understanding How Inherited DNA Variations Influence Blood Cancer Development