Next Generation Large Animal Oncology Preclinical Transitional Platform: Developing New Approach Methodologies and Emerging Regulatory Considerations
Main Article Content
Abstract
Preclinical cancer models are essential for assessing the safety and efficacy of new therapeutics. The goals of this review are to address the development of an in vivo cancer technology platform that provides a tool for addressing emerging preclinical regulatory processes required for advancing new therapeutics and devices for use into the clinic. Previous studies have established the utility of porcine models as an alternative large animal model for cancer research due to their similarity to human size, genetics, metabolism, and physiology. Additionally, tumorigenesis pathways are similar between human and pigs in that similar driver mutations are required for transformation. Due to their larger size porcine models can be harnessed for testing of new interventional devices and radiological/surgical approaches as well. Taken together, swine are a feasible option for preclinical therapeutic and device testing. This review provides insights into the value of in vivo porcine models to provide both toxicity and efficacy data to support pre-clinical trials. The article describes next generation large animal models for cancer research, focusing on how genetically engineered pigs—particularly the Oncopig® and mini-Oncopig can bridge the gap between lab experiments and real-world human clinical trials. Evidence is provided to demonstrate how these models address major shortcomings of traditional methods and help accelerate safe and effective cancer treatment development. The inducible transgenic Oncopig and mini-Oncopig develop site and cell and driver mutation specific tumors for preclinical human cancer that supports preclinical evaluation of novel drugs, biologicals, devices and locoregional therapies. The Wisconsin Mini-swine-Oncopig is a minipig nutritionally inducible metabolic diseases (fatty liver disease and obesity) in a small animal applicable for pharmaceutical evaluation. A final and important goal of this review is to demonstrate that such cancer models are consistent with the 3-Rs and support emerging new approach methodologies evaluations.
Keywords:
NAMs, AI, Oncopigs, mini-Oncopigs, safety and efficacy platforms, precision medicine
Article Details
How to Cite
SCHACHTSCHNEIDER, Kyle M. et al.
Next Generation Large Animal Oncology Preclinical Transitional Platform: Developing New Approach Methodologies and Emerging Regulatory Considerations.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7194>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7194.
Section
Review 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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3. 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
4. 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
5. 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
6. 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
7. 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
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. Schachtschneider KM, Mehta V, Rege J, Schook LB. Oncopigs: an inducible transgenic large animal cancer model to address pre-clinical assessments. Medical Research Archives. 2025-03-29 2025;13(3)doi:10.18103/mra.v13i3.6392
10. Schachtschneider KM, Jungersen G, Schook LB, Shanmuganayagam D. Editorial: "Humanized" Large Animal Cancer Models: Accelerating Time and Effectiveness of Clinical Trials. Front Oncol. 2019;9:793. doi:10.3389/fonc.2019.00793
11. Schachtschneider KM, Redlon LN, Lokken RP, et al. Epigenetic regulation of individual components of combined hepatocellular-cholangiocarcinoma. PLoS One. 2025;20(5):e0324145. doi:10.1371/journal.pone.0324145
12. 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
13. 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/fonc.2017.00190
14. 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
15. 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
16. 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
17. Gaba RC, Elkhadragy L, Boas FE, et al. Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation. Oncotarget. Jul 14 2020;11(28):2686-2701. doi:10.18632/oncotarget.27647
18. 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.jvir.2018.12.279
19. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. May 2021;71(3):209-249. doi:10.3322/caac.21660
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