Oncopigs: an inducible transgenic large animal cancer model to address pre-clinical assessments
Main Article Content
Abstract
Cancer research progress has been markedly hampered by the lack of clinically relevant systems in which to study the effects of mutational interactions on cancer phenotypes. To address this, we developed an inducible transgenic Oncopig®, a unique genotypically, anatomically, metabolically, and physiologically relevant large animal model that develops inducible site and cell specific tumors for preclinical study of human cancer. The Oncopig® harbors mutations found in >50% of human cancers- KRASG12D and TP53R167H- and results in tumors that recapitulate the phenotype and physiology of human cancers. As in human disease, TERT is solely expressed in Oncopig® cancer cells, and innate Oncopig® KRASG12D and TP53R167H driver mutations are heterozygous in nature. The Oncopig® size allows utilization of the same interventional tools, such as radiological, imaging and surgical devices all employed in human clinical practice. The Oncopig® is also an ideal model for investigation of drug toxicity, as its basal metabolic rate and xenosensor pregnane X receptor homology and functionality (responsible for the metabolism of half of all prescription drugs) are also very similar to humans. In addition, we have demonstrated the ability to genetically engineer Oncopig® cell lines to facilitate the controlled addition of gene mutations in induced tumors for improved preclinical investigation of the impact of cancer phenotypes on diagnostic and therapeutic approaches. Therefore, the Oncopig Cancer Model® fulfills current unmet clinical modeling, needs as the only FDA cleared large animal cancer model, that supports device, drug and diagnostic safety, risk and efficacy studies. (238 words)
Keywords:
Oncopig®, large-animal, pre-clinical, safety, and efficacy
Article Details
How to Cite
SCHACHTSCHNEIDER, Kyle M. et al.
Oncopigs: an inducible transgenic large animal cancer model to address pre-clinical assessments.
Medical Research Archives, [S.l.], v. 13, n. 3, mar. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6392>. Date accessed: 06 apr. 2025.
doi: https://doi.org/10.18103/mra.v3i3.6392.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Honkala A, Malhotra SV, Kummar S, Junttila MR. Harnessing the predictive power of preclinical models for oncology drug development. Nature Reviews Drug Discovery. 2022/02/01 2022;21(2): 99-114. doi:10.1038/s41573-021-00301-6
3. Bryda EC. The Mighty Mouse: the impact of rodents on advances in biomedical research. Mo Med. May-Jun 2013;110(3):207-11.
4. Onaciu A, Munteanu R, Munteanu VC, et al. Spontaneous and Induced Animal Models for Cancer Research. Diagnostics (Basel). Aug 31 2020;10(9) doi:10.3390/diagnostics10090660
5. Sajjad H, Imtiaz S, Noor T, Siddiqui YH, Sajjad A, Zia M. Cancer models in preclinical research: A chronicle review of advancement in effective cancer research. Animal Model Exp Med. Jun 2021;4(2):87-103. doi:10.1002/ame2.12165
6. Schook L, Beattie C, Beever J, et al. Swine in biomedical research: creating the building blocks of animal models. Anim Biotechnol. 2005;16(2): 183-90. doi:10.1080/10495390500265034
7. Hou N, Du X, Wu S. Advances in pig models of human diseases. Animal Model Exp Med. Apr 2022;5(2):141-152. doi:10.1002/ame2.12223
8. Meyerholz DK, Burrough ER, Kirchhof N, Anderson DJ, Helke KL. Swine models in translational research and medicine. Vet Pathol. Jul 2024;61(4):512-523. doi:10.1177/03009858231222235
9. Schook LB, Collares TV, Darfour-Oduro KA, et al. Unraveling the swine genome: implications for human health. Annu Rev Anim Biosci. 2015;3: 219-44. doi:10.1146/annurev-animal-022114-110815
10. Groenen MAM, Archibald AL, Uenishi H, et al. Analyses of pig genomes provide insight into porcine demography and evolution. Nature. 2012/ 11/01 2012;491(7424):393-398. doi:10.1038/natur e11622
11. Schachtschneider KM, Schwind RM, Darfour-Oduro KA, et al. A validated, transitional and translational porcine model of hepatocellular carcinoma. Oncotarget. Sep 8 2017;8(38):63620-63634. doi:10.18632/oncotarget.18872
12. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. Mar 10 2005;352(10):987-96. doi:10.1056/NEJMo a043330
13. de Jong M, Maina T. Of mice and humans: are they the same?--Implications in cancer translational research. J Nucl Med. Apr 2010;51(4):501-4. doi:10.2967/jnumed.109.065706
14. Hicks WH, Bird CE, Pernik MN, et al. Large Animal Models of Glioma: Current Status and Future Prospects. Anticancer Res. Nov 2021;41 (11):5343-5353. doi:10.21873/anticanres.15347
15. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell. Aug 14 2017;32(2):185-203.e13. doi:10.1016/j.cce ll.2017.07.007
16. Connor AA, Denroche RE, Jang GH, et al. Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases. Cancer Cell. Feb 11 2019;35(2):267-282.e7. doi:10.1016/j.ccel l.2018.12.010
17. Aravalli RN, Golzarian J, Cressman EN. Animal models of cancer in interventional radiology. Eur Radiol. May 2009;19(5):1049-53. doi:10.1007/s00330-008-1263-8
18. Overgaard NH, Fan TM, Schachtschneider KM, Principe DR, Schook LB, Jungersen G. Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research. Ilar j. Dec 31 2018;59(3):247-262. doi:10.1093/ilar/ily014
19. Pollock CB, Rogatcheva MB, Schook LB. Comparative genomics of xenobiotic metabolism: a porcine-human PXR gene comparison. Mamm Genome. Mar 2007;18(3):210-9. doi:10.1007/s00335-007-9007-7
20. Schook LB, Collares TV, Hu W, et al. A Genetic Porcine Model of Cancer. PLoS One. 2015;10(7):
e0128864. doi:10.1371/journal.pone.0128864
21. Elkhadragy L, Gaba RC, Niemeyer MM, Schook LB, Schachtschneider KM. Translational Relevance and Future Integration of the Oncopig® Cancer Model in Preclinical Applications. Annu Rev Anim Biosci. Oct 17 2024;doi:10.1146/annurev-animal-111523-102125
22. Joshi K, Telugu BP, Prather RS, et al. Benefits and opportunities of the transgenic Oncopig® cancer model. Trends Cancer. Mar 2024;10(3):182-184. doi:10.1016/j.trecan.2024.01.005
23. Robertson N, Schook LB, Schachtschneider KM. Porcine cancer models: potential tools to enhance cancer drug trials. Expert Opin Drug Discov. Aug 2020;15(8):893-902. doi:10.1080/17460441.2 020.1757644
24. Schachtschneider KM, Schwind RM, Newson J, et al. The Oncopig® Cancer Model: An Innovative Large Animal Translational Oncology Platform. Front Oncol. 2017;7:190. doi:10.3389/fo nc.2017.00190
25. Lobianco F, Giurini E, Neto M, et al. 03:27 PM Abstract No. 221 Porcine and human hepatocellular carcinoma cell lines present similar drug-metabolizing enzyme expression levels and comparable sorafenib and doxorubicin cytotoxic responses. Journal of Vascular and Interventional Radiology. 2019;30 (3):S99-S100. doi:10.1016/j.jvi r.2018.12.279
26. Xu C, Wu S, Schook LB, Schachtschneider KM. Translating Human Cancer Sequences Into Personalized Porcine Cancer Models. Front Oncol. 2019;9:105. doi:10.3389/fonc.2019.00105
27. Singhal M, Khatibeghdami M, Principe DR, et al. TM4SF18 is aberrantly expressed in pancreatic cancer and regulates cell growth. PLoS One. 2019; 14(3):e0211711. doi:10.1371/journal.pone.0211711
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