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Clinical Research Programme

Prostate Cancer Clinical Research Unit

Head of Unit:  David Olmos
Overview

Prostate cancer (PrCa) is one of the most heritable human cancers, as almost 60% of the PrCa risk is attributable to genetic factors. Inherited mutations in several genes involved in DNA damage response and repair (DDR) have been reported to predispose men to prostate cancer; this includes mutations in BRCA2, the genetic event known to confer the greatest risk of the disease. Recent studies have revealed that germline deleterious mutations in DDR genes are present in 8-12% of patients with metastatic PrCa, mutations in BRCA2 being the most prevalent ones. Our Group has previously established that these mutations are an independent prognostic factor for the disease. These observations have come full-circle with the development of Poly (ADP-ribose) polymerase inhibitors to treat advanced prostate cancer. Due to the high prevalence of DDR germline mutations and the implications for the patients and their families, clinical guidelines have recently been updated to recommend genetic screening to all patients with metastatic PrCa. In consequence, the number of mutation carriers is likely to grow over the next few years, whilst the most appropriate treatment and management still remains unknown. This year our Unit’s research has focussed on gaining a better understanding of the clinical implications of BRCA2 and other DDR defects ; the molecular characterisation of these tumours and the identification of biomarkers can enable us to predict the benefit derived from currently available therapies.