Genetically Engineered Pigs to Study Cancer

Abstract

Recent decades have seen groundbreaking advances in cancer research. Genetically engineered animal models, mainly in mice, have contributed to a better understanding of the underlying mechanisms involved in cancer. However, mice are not ideal for translating basic research into studies closer to the clinic. There is a need for complementary information provided by non-rodent species. Pigs are well suited for translational biomedical research as they share many similarities with humans such as body and organ size, aspects of anatomy, physiology and pathophysiology and can provide valuable means of developing and testing novel diagnostic and therapeutic procedures. Porcine oncology is a new field, but it is clear that replication of key oncogenic mutation in pigs can usefully mimic several human cancers. This review briefly outlines the technology used to generate genetically modified pigs, provides an overview of existing cancer models, their applications and how the field may develop in the near future.

Keywords: breast cancer; colorectal cancer; genome editing; osteosarcoma; pancreatic cancer; pig; preclinical cancer models; swine; transgenic.

Figure 1

The pig as a biomedical model. Pigs can help translate basic research findings into new medical drugs and procedures; ‘bridging the gap between bench and bedside’.

Figure 2

Phenotype of adenomatous polyposis coli (APC)¹³¹¹ pigs. Polyp progression during the first 24 months.

Figure 3

Porcine cancer models. These can be established by different methods: e.g., introduction of oncogenic germline mutations or via genome editing in organs of a Cas9 pig. Biopsies taken early in life can be oncogenically transformed and reimplanted into the same pig. If isolated from a pig with latent oncogenic mutations, these can be activated in vitro prior to implantation. Human tumor samples can also be implanted in immune deficient animals.