Pre-Clinical Models to Study Human Prostate Cancer.

Area of Science:

• Oncology
• Genetics
• Animal Models

Background:

• Prostate cancer is a prevalent malignancy in men, often progressing slowly before becoming aggressive.
• While canine models offer anatomical similarity, mouse models are preferred for genetic manipulation in prostate cancer research.
• The identification of the Probasin promoter was crucial for enabling prostate-specific gene expression in mice.

Purpose of the Study:

• To review advances in preclinical models for prostate cancer research.
• To highlight techniques enabling the study of prostate cancer mechanisms and the development of new treatments.

Main Methods:

• Utilizing the Probasin promoter for prostate-specific transgene and Cre expression in genetically modified mice.
• Employing orthotopic viral particle delivery for oncogene overexpression and CRISPR-mediated loss-of-function studies.
• Complementing genetically engineered models with classical xenografts of human prostate tumor cells in immune-deficient mice.

Main Results:

• Genetically modified mouse models now allow for the creation of aggressive prostatic tumors via oncogene overexpression (e.g., SV40).
• Prostate-specific loss-of-function studies are feasible through Probasin promoter-driven Cre expression.
• Orthotopic viral delivery enables selective oncogene overexpression and complex genetic modifications using CRISPR.

Conclusions:

• Preclinical models, particularly genetically modified mice, offer a robust platform for investigating complex prostate cancer biology.
• Advances in genetic engineering and delivery methods have significantly enhanced the utility of mouse models for cancer research.
• These sophisticated models are vital for addressing challenges in prostate cancer and improving therapeutic strategies.