Men with low to intermediate risk prostate cancer (PCa) face vexing decisions regarding treatment. The tumour can remain indolent and will not impact the patient within his lifetime, or it can progress to become life threatening (metastatic tumour). A holy grail of PCa research is the identification of prognostic biomarkers, which are biological factors that are associated with the disease outcomes, that can be used to improve patient risk stratification at time of diagnosis and guide treatment decisions. We have created patient-derived PCa tumour mouse models with different metastatic potential that fully recapitulate the transition of a patient tumour from indolence to metastasis. In an effort to identify the mechanisms that drive the growth of a metastatic tumour in these models, we have identified a rich source of prognostic biomarkers in the mouse stroma, which is the tissue supporting tumour growth. We have been able to identify a group of 93 genes only active in the mouse stroma associated with metastasis. We called this group of genes the Stromal Metastatic Signature or SMS. In collaboration with GenomeDx Biosciences, a Vancouver-based company, we confirmed our preliminary observations; that the SMS is strongly prognostic for predicting metastasis in human tumour. The purpose of this very innovative proposal is to seek funding first to further validate the SMS using additional large human tumour cohorts, second to improve the SMS prognostic value by integrating existing tumour-based signatures, and finally to test the hypothesis that the stromal compartment drives metastasis using a novel therapeutic agent developed in our research centre. This very innovative project represents a unique opportunity to apply novel and exciting research findings to the advancement of an important health issue.

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