The role of murine models of prostate cancer in drug target discovery and validation

Abstract

Background: Mice provide us with an excellent preclinical model of human prostate cancer. They have expanded our understanding of the molecular pathways involved in prostate carcinogenesis as well as allowing us to explore both novel and traditional treatment regimes based on the molecular profile of these lesions. Continuing refinement of the transgenic prostate models has proven challenging since no one model seems to represent the entire continuum of the disease, thus currently limiting its applicability to the human condition. This platform may potentially have major impact in validation of drug targeting specific biological process of prostate carcinogenesis, supplementing (or even replacing) many of the current in vitro and in vivo assays with the in vivo environment that transgenic prostate models provide. Objective/method: This review focuses primarily on the current state of murine model systems as a preclinical therapeutic platform for the treatment of prostate cancer, as well as hope for the future of the field. Conclusion: Much of the work in the drug discovery field has been done with the PTEN^-/- and TRAMP models of prostate cancer. Despite their limitations they have contributed much to our understanding of the pathophysiology of the disease. There is, however, a need for transgenic models that better reflect the stepwise progression found in the human condition. We feel that they will prove to be invaluable as a preclinical platform regarding efficacy and tolerability of various anticancer agents, which ultimately allows us to translate these findings to the clinical setting to prognosticate and ultimately render cancer patients disease-free.

Keywords::

• drug discovery
• GFP
• mouse models
• prostate cancer
• PTEN

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