Annually, over 200 000 new prostate cancer cases are diagnosed in Europe. This number is expected to further increase due to widespread use of prostate specific antigen (PSA) tests on asymptomatic men and an aging population. This leads to high rate of over-detection, where most cases will never experience cancer symptoms during their lifetime. Hence, our current lack of means to predict prostate cancer prognosis will have devastating impact on both life-quality and health care expenditures. Molecular mechanisms of the development of prostate cancer are largely unknown apart from the recognized role of androgens. Lack of knowledge on mechanisms leading to the development and progression of this cancer hampers development of efficacious prevention, specific diagnostics, prognostic, and therapeutic tools. Based on the emerging knowledge on the function of non-coding RNAs (ncRNAs) as regulators of key cellular mechanisms and our own preliminary data on expression of ncRNAs in prostate cancer, it is very likely that ncRNAs are involved in the tumorigenesis and progression of prostate cancer. Our planned studies of ncRNAs can contribute major breakthroughs to optimize individualized prostate cancer treatment by providing both novel biomarkers and drug targets. In this project, we will pursue two major clinical problems: 1) early identification of cases requiring aggressive curative treatment, and 2) develop efficient therapies against hormone-refractory prostate cancer. The project will cover all phases of translational research, from discovery to validation and implementation. We will identify novel ncRNAs, investigate their expression, genetic/epigenetic alterations, and function. We will develop diagnostic tools, identify and validate therapeutic targets. To assure the success of the project, our consortium consists of leading translational prostate cancer research centers in Europe and companies committed to develop ncRNA detection technologies and novel drugs.