Drug discovery in prostate cancer mouse models

Abstract

Introduction The mouse is an important, though imperfect, organism with which to model human disease and to discover and test novel drugs in a preclinical setting. Many experimental strategies have been used to discover new biological and molecular targets in the mouse, with the hopes of translating these discoveries into novel drugs to treat prostate cancer in humans. Modeling prostate cancer in the mouse, however, has been challenging, and often drugs that work in mice have failed in human trials. Areas covered Here we discuss similarities and differences between mice and men, types of mouse models that exist to model prostate cancer, practical questions one must ask when using a mouse as a model, and potential reasons that drugs do not often translate to humans. We will also discuss the current value in using mouse models for drug discovery to treat prostate cancer and what needs are still unmet in field. Expert opinion With proper planning and following practical guidelines by the researcher, the mouse is a powerful experimental tool. The field lacks genetically engineered metastatic models, and xenograft models do not allow for the study of the immune system during the metastatic process. There remain several important limitations to discovering and testing novel drugs in mice for eventual human use, but these can often be overcome. Overall, mouse modeling is an essential part of prostate cancer research and drug discovery. Emerging technologies and better and ever-increasing forms of communication are moving the field in a hopeful direction.

Disparities in prostate cancer incidence and mortality rates: Solvable or not?

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Deletion of tumor suppressors adenomatous polyposis coli and Smad4 in murine luminal epithelial cells causes invasive prostate cancer and loss of androgen receptor expression

“…Multiple genetic pathways are involved in the tumorigenesis of the prostate [ 3 , 18 – 21 ]. Due to this heterogeneity – as well as the normal physiological differences between human and mouse prostates [ 22 , 23 ] – it has been difficult to create a mouse model that fully recapitulates human prostate cancer progression. Many genetically engineered models have been made, each one representing some aspect of prostate cancer, and contributing to the library of knowledge on the effect of each gene(s) on prostate tumorigenesis and progression [ 22 ].…”

Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research

“…When taking a closer look at the most extensively used animal in PC research, the mouse, there are several disadvantages that may explain why so few drugs that work in mice do not work in humans. With regard to prostate gene expression, while both mouse and human prostate cells respond to androgen stimulation and signaling [136], the expression of certain human androgen-responsive genes (e.g., prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA)) is not present in mice [137][138][139]. When analyzing the prostates of mice and men, they significantly differ anatomically.…”