Pre-Clinical Models to Study Human Prostate Cancer

SIMPLE SUMMARY: The incidence of prostate cancer is rising, primarily due to its prevalence among elderly men, and with increased life expectancy, these numbers are expected to continue increasing. Prostate cancer can remain indolent for many years, but treatment options are limited once the cancer progresses to an aggressive stage. Pre-clinical models have played a vital role in gaining insights into this particular cancer, revealing essential information about the molecular alterations that drive cancer progression. The mouse model has been invaluable for studying prostate cancer, employing both genetically modified strains and the inoculation of prostate cancer cells. This review will focus on the development of pre-clinical models for studying prostate cancer and discuss future directions for enhancing our understanding and developing interventions for prostate cancer. ABSTRACT: Prostate cancer is a common cancer among men and typically progresses slowly for several decades before becoming aggressive and spreading to other organs, leaving few treatment options. While large animals have been studied, the dog’s prostate is anatomically similar to humans and has been used to study spontaneous prostate cancer. However, most research currently focuses on the mouse as a model organism due to the ability to genetically modify their prostatic tissues for molecular analysis. One milestone in this research was the identification of the prostate-specific promoter Probasin, which allowed for the prostate-specific expression of transgenes. This has led to the generation of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and has allowed researchers to generate prostate-specific loss-of-function studies. Another landmark moment in the process of modeling prostate cancer in mice was the orthoptic delivery of viral particles. This technology allows the selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss-of-function studies. These genetically modified models are complemented by classical xenografts of human prostate tumor cells in immune-deficient mice. Overall, pre-clinical models have provided a portfolio of model systems to study and address complex mechanisms in prostate cancer for improved treatment options. This review will focus on the advances in each technique.