title: 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.
authors.affiliation: Department of Surgery/Urology, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hensley
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D059016:Tumor Microenvironment