Modeling Prostate Cancer in Mice: Limitations and Opportunities

Abstract

The complex dynamics of the tumor microenvironment and prostate cancer heterogeneity have confounded efforts to establish suitable preclinical mouse models to represent human cancer progression from early proliferative phenotypes to aggressive, androgen-independent, and invasive metastatic tumors. Current models have been successful in capitulating individual characteristics of the aggressive tumors. However, none of these models comprehensively mimics human cancer progression, establishing the challenge in their exploitation to study human disease. The ability to tailor phenotypic outcomes in mice by compounding mutations to target specific molecular pathways provides a powerful tool toward disruption of signaling pathways contributing to the initiation and progression of castration-resistant prostate cancer. Each model is characterized by unique features contributing to the understanding of prostate tumorigenesis, as well as limitations challenging our knowledge of the mechanisms of cancer development and progression. Emerging strategies utilize genomic manipulation technology to circumvent these limitations toward the formulation of attractive, physiologically relevant models of prostate cancer progression to advanced disease. This review discusses the current value of the widely used and well-characterized mouse models of prostate cancer progression to metastasis, as well as the opportunities begging exploitation for the development of new models for testing the antitumor efficacy of therapeutic strategies and identifying new biomarkers of disease progression.

Animal Models of Bone Metastasis

“…54 Only the TRAMP X FBV mice are reported to uncommonly develop bone metastases with a minimal osteolytic/osteoblastic response to the neoplastic cells. 35,37,45,112 …”

Key participants of the tumor microenvironment of the prostate: An approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial–stromal transition

“…Currently, preclinical models of prostate cancer in major use include those derived from rat, dog, mouse, and human sources (Pienta et al, 2008). Each model is characterized by unique features contributing to the understanding of prostate tumorigenesis, as well as limitations challenging our knowledge of the mechanisms of cancer development and progression (Pienta et al, 2008;Hensley and Kyprianou, 2012;Zou et al, 2013).…”

WITHDRAWN: Mechanisms navigating the TGF-β pathway in prostate cancer

“…The Pten knockout, the Nkx3.1 knockout, the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model and probasin-large T-antigen transgenic mouse (LADY) model have been established and effectively exploited [70]. Work from this laboratory demonstrated that dominant-negative mutant TGF-bRII receptor accelerates prostate tumorigenesis in the TRAMP mouse model by enhancing EMT and disrupting the growth kinetics within the tumor microenvironment [27].…”