Grant: Operating Grant

Prostate cancer ranks as third biggest cancer-killer of men, with over 4,000 Canadian men expected to die of this disease this year. Primary tumours rarely kill patients directly, but often shed malignant cells that are able to seed new tumours at distant sites within the body such as in the bone marrow. These new tumours, called "metastases", are responsible for 90% of cancer deaths. In most cases, the cancer cells must enter and circulate in the bloodstream before seeding a secondary tumour, with the circulating tumour cells, or "CTCs" as they are usually referred to, generally considered a necessary pre-condition and predictor for the occurrence of distant metastases. Finding new sensitive methods for very early detection of cancer dissemination before full blown, clinical metastases are evident should allow quicker intervention and hence save lives. The Veridex CellSearch system is the only FDA-approved method for clinical monitoring of CTCs, but it requires very expensive equipment and a dedicated operator which many hospitals and cancer centers cannot easily afford. Also this system relies on a cell surface marker, which may not be universally expressed on all tumour cells. Accordingly, the primary objective of our proposed project is to develop new, highly sensitive, inexpensive and readily accessible methods for accurately measuring the presence of CTCs at the earliest possible time. To achieve this, we will test three very novel, virus-based methods to detect and quantify CTCs in small blood samples taken from the patient: a direct measure of a virus-induced fluorescent protein marker in CTCs and two super-sensitive indirect methods using a secretable enzyme and immune response markers to gauge the number of CTCs. These new assays should provide an opportunity for earlier detection and treatment of metastases which should translate into increased survival for patients with advanced, metastatic prostate cancer.