Abstract
Swine biomedical models have been gaining in popularity over the last decade, particularly for applications in oncology research. Swine models for cancer research include pigs that have severe combined immunodeficiency for xenotransplantation studies, genetically modified swine models which are capable of developing tumors in vivo, as well as normal immunocompetent pigs. In recent years, there has been a low success rate for the approval of new oncological therapeutics in clinical trials. The two leading reasons for these failures are either due to toxicity and safety issues or lack of efficacy. As all therapeutics must be tested within animal models prior to clinical testing, there are opportunities to expand the ability to assess efficacy and toxicity profiles within the preclinical testing phases of new therapeutics. Most preclinical in vivo testing is performed in mice, canines, and non-human primates. However, swine models are an alternative large animal model for cancer research with similarity to human size, genetics, 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, the development of orthotopic tumors is easier than in smaller rodent models; additionally, 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. The goals of this resource are to provide a broad overview on regulatory processes required for new therapeutics and devices for use in the clinic, cross-species differences in oncological therapeutic responses, as well as to provide an overview of swine oncology models that have been developed that could be used for preclinical testing to fulfill regulatory requirements.
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This project was funded by the Office of the Director, the Office of Research Infrastructure Programs, and the National Institutes of Health 5R24OD028748-02.
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KS receives research funding from Guerbet United States LLC, NeoTherma Oncology, and Janssen Research Development LLC. KS is a scientific consultant for Sus Clinicals, Inc. LBS receives research funding from Guerbet United States LLC, and NeoTherma Oncology. LBS is CSO for Sus Clinicals, Inc.
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Boettcher, A.N., Schachtschneider, K.M., Schook, L.B. et al. Swine models for translational oncological research: an evolving landscape and regulatory considerations. Mamm Genome 33, 230–240 (2022). https://doi.org/10.1007/s00335-021-09907-y
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DOI: https://doi.org/10.1007/s00335-021-09907-y