The Genomic Drivers of High Risk Prostate cancer

Summary The issue of prostate cancer (CaP) in the Western world represents a major clinical problem with the prostate being the most cancer prone internal organ, but only an unpredictable 10% of these cases progress to lethality.

Project Details

Nearly all lethal cases are linked with metastasis and subsequent emergence of therapy resistant disease. Multiple genomic studies have now attempted to ascertain molecular subtypes of prostate cancer, however these studies have been hampered by a lack of matching clinical follow up data and lacked the power to detect low level but clinically meaningful aberrations. So far none of the defined molecular subtypes could be linked with any clinically relevant patient outcomes. We have now performed an intensive whole genomic analysis of the largest cohort of patients with prostate cancer ever assembled to date. This data spans the spectrum of high risk disease, enriched with metastatic events, combined with an expanded low-intermediate risk cohort and our analysis is yielding new prognostic biomarkers which can discriminate between low and high risk disease. We have already amassed and whole genome sequenced this cohort of 550 tumours, all with comprehensive and ongoing clinical follow up. Our aim is now to take these differential signature sets and design targeted capture probes and interrogate non-invasive liquid biopsies harvested from prostate cancer patients. We will then formally determine whether these signatures can quantifiably measure ctDNA in plasma and blood in a 3 staged approach on independent cohorts of patients and derive proof of principle evidence that this approach can screen early stage patients with high risk disease features.

Skills & Techniques may involve: tissue culture, western blotting, immunohistochemistry, RNA/DNA extraction, qPCR, work on animal models, drug screening, FACS, Datamining.

Benefits to student: Molecular and clinical research, multi-collaborative project encompassing basic research and clinical interaction.

Research students will work within a team of experienced scientists and have access to scientific expertise and equipment through our department, associated institutions and existing collaborations with leading urologists.