“Humanized” Large Animal Cancer Models: Accelerating Time and Effectiveness of Clinical Trials

This Frontiers in Oncology Research Topic provides futuristic perspectives with respect to the emerging requirements of large animal cancer models to address unmet clinical needs. As the vast majority of drugs tested in small animal cancer models fail in human clinical trials, there is a need for large animal models to translate results obtained in small animal models to human clinical practice. In addition, the majority of preclinical immunotherapy studies conducted in rodents have translated poorly to the clinic due to substantial differences between murine and human immunology. As the porcine and canine immune systems display substantial homology to that of humans, these large animals represent excellent platforms for preclinical investigation of cancer immunotherapies. Utilization of large animal models also allows for testing of the same devices and tools used in human clinical practice in species with similar size, anatomy, physiology, metabolism, immunology, and genetics compared to humans. The continued development of genomic and phenomic tools and databases also provides the ability through genome editing to create “humanized” experimental large animal models that can support interventional targeted cancer drug and device development.

Contributions will provide insights into conceptualizing from experimental models (mouse and pig) to spontaneous disease (dog and human) clients to avoid gaps and increase therapeutic value. The scope of topics includes the development of large animal clinical trial networks, incorporating FDA requirements into creating experimental and spontaneous validated/qualified alternative clinical models. The ability to produce experimental animals that exhibit clinically relevant comorbidities through either experimental approaches or crossing animals with fixed phenotypes will also be covered. Relevant targeted comorbidities include alcohol-induced cirrhosis, nonalcoholic steatohepatitis (NASH), diabetes, obesity, and cardiovascular disease. In addition, both experimental (porcine) and spontaneous (canine) large animal cancer models are being recognized by the National Cancer Institute as valuable tools for testing of drugs and devices in co-clinical trials; hence reducing the accrual time for launching a human clinical trial. However, there are also clinical gaps in expertise that need to be addressed in order to fully realize the power of co-clinical trials. This Research Topic will also address training needs with regards to comparative pathology and the development of imaging standards to support relevant interpretation of findings and expedite the launch of human clinical trials.