Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Prostate cancer (PCa) remains the most common malignancy in Canadian men, with 1 in 7 diagnosed during their lifetime, causing 4,300 deaths/year. Despite being an often slow-growing disease, PCa can threaten patients` lives by its ability to overcome initial therapies, leading to metastasis and therefore yielding a poor prognosis. PCa patients can expect high survival rates, as long as their cancer remains local. Early detection and effective diagnostics are though critical. To date, the only blood marker for PCa is the prostate specific antigen (PSA). A recent controversy surrounding the PSA suggests its limited usefulness as an early diagnostic screening test as PSA is sensitive but has many limitations, including that it is not specific for PCa and cannot discriminate between indolent and non-indolent cancers. As a result, once PSA levels are abnormal, men may face potential unnecessary treatment. For these reasons, new biomarkers are required. For most cancers, the use of positron-emission tomography (PET) for tumor and metastases as become an important tool for cancer diagnostic. However, unlike other tumor types, PCa tumors are not diagnosable by the currently used PET metabolic tracers because of their poor metabolic turnover compared to benign tissues. The discovery of novel marker targetable with PET tracers is imperative to allow reliable early tumor diagnosis. Recently, substantial evidence has been uncovered for the role of a family of enzymes known as the proprotein convertases in cancer. PCa cells markedly up-regulate their expression of PACE4, to such an extent that it is also detected in the serum. Recent studies which I took part of showed that 100% of post-surgical PCa examined overexpressed PACE4 and that the levels of PACE4 (3-30x increase correlating with disease severity). We propose that PACE4 is a valuable marker of PCa, that could complement PSA and I am currently developing a tracer targeting PACE4, which allow PCa detection by PET.