Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Pre-Clinical Models to Study Human Prostate Cancer

Version 1 : Received: 20 July 2023 / Approved: 20 July 2023 / Online: 21 July 2023 (07:36:00 CEST)

A peer-reviewed article of this Preprint also exists.

Thomsen, M.K.; Busk, M. Pre-Clinical Models to Study Human Prostate Cancer. Cancers 2023, 15, 4212. Thomsen, M.K.; Busk, M. Pre-Clinical Models to Study Human Prostate Cancer. Cancers 2023, 15, 4212.

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 hallmark in this research was the identification of the prostate-specific promoter Probasin, allowing for prostate-specific expression of transgenes. This has led to generations of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and allow researcher to generated prostate specific loss-of-function studies. Another landmark in the process of modeling prostate cancer in mice was orthoptic delivery of viral particles. This technology allows selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss of function studies. These genetic 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 of each technique.

Keywords

prostate cancer; mouse model; xenograft; PDX; CRISPR; probasin

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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