The Oncopig Cancer Model as a Complementary Tool for Phenotypic Drug Discovery

Natalia V. Segatto, Mariana H. Remião, Kyle M. Schachtschneider, Fabiana K. Seixas, Lawrence B. Schook, Tiago Collares

The screening of potential therapeutic compounds using phenotypic drug discovery (PDD) is being embraced once again by researchers and pharmaceutical companies as an approach to enhance the development of new effective therapeutics. Before the genomics and molecular biology era and the consecutive emergence of targeted-drug discovery approaches, PDD was the most common platform used for drug discovery. PDD, also known as phenotypic screening, consists of screening potential compounds in either in vitro cellular or in vivo animal models to identify compounds resulting in a desirable phenotypic change. Using this approach, the biological targets of the compounds are not taken into consideration. Suitable animal models are crucial for the continued validation and discovery of new drugs, as compounds displaying promising results in phenotypic in vitro cell-based and in vivo small animal model screenings often fail in clinical trials. Indeed, this is mainly a result of differential anatomy, physiology, metabolism, immunology, and genetics between humans and currently used pre-clinical small animal models. In contrast, pigs are more predictive of therapeutic treatment outcomes in humans than rodents. In addition, pigs provide an ideal platform to study cancer due to their similarities with humans at the anatomical, physiological, metabolic, and genetic levels. Here we provide a mini-review on the reemergence of PDD in drug development, highlighting the potential of porcine cancer models for improving pre-clinical drug discovery and testing. We also present precision medicine based genetically defined swine cancer models developed to date and their potential as biomedical models.