Rapid Cap: A new generation of mouse models for prostate cancer

Genetically Engineered Mouse Models are the gold standard for functional cancer research. However, the associated time and cost requirements severely limit their application. As a consequence, projects carry typically a high risk, are lengthy, and scientists become ‘locked in’ with a few chosen candidate alterations. To realize the full potential of mouse modeling technology we have developed RapidCaP, a system that relies on surgical gene transfer. Through prostate specific delivery of transgenic virus we can 1) reduce model generation times from several years to a few weeks, 2) test various genetic alterations such as loss or gain of function, alone or in combination, and 3) use non-invasive imaging to monitor disease progression. Using RapidCaP, we show that focal loss of Pten and Trp53 genes triggers prostate lesions within 2 months. Furthermore, we find that this disease responds to castration by strong regression within several weeks, but it later relapses to produce lethal hormone refractory disease. Taken together, our approach establishes a novel platform for basic prostate cancer research and it realizes the goal of carrying out pre-clinical studies in genetically engineered mice.