Characterizing and Validating the Oncopig Cancer Model for Treatment of Lung Tumors

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related mortality, underscoring the need for innovative diagnostics and therapeutics to alleviate the global lung cancer burden. The Oncopig Cancer Model, a transgenic pig model expressing heterozygous KRASG12D and TP53R167H mutations, offers several advantages for translational research due to its anatomical and physiological similarities to humans. However, much remains unknown regarding how the Oncopig lung cancer model relates to humans. Lung tissues from ten Oncopigs (6 controls and 4 interventions) were analyzed. Characterization of both the radiologic and histologic phenotypes of the lung tumors found some congruency with human lung adenocarcinoma. Transcriptional profiling subsequently identified key genes, such as TNFα, HIF1A, EGFR, and MYC. Their respective tumor pathways were also compared to common human lung tumor pathways. As anticipated, pathways involved in immune mediation, tumor growth, and metabolism were among the most often activated. Nevertheless, further research and directions can be explored. Future work should include multiple control pig sampling, increased statistical power, and control for variables such as carcinogen exposure and age to enhance the model's robustness and utility in preclinical testing.