ABSTRACT

Improvements in screening and treatment have led to a steady decline in mortality from prostate cancer over the past 10 years. Yet prostate cancer remains a leading cause of death among European and North American men over 501. Localized tumors can be removed by radical surgery or destroyed by radiotherapy, but almost 40% of patients already have occult metastases that necessitate second-line therapy. Since the work of Huggins and colleagues in the 1940s2, androgen withdrawal, aimed at triggering hormone-dependent apoptosis of the prostatic epithelium, has been the cornerstone of treatment for advanced, metastatic prostate adenocarcinomas. However, patients who relapse during hormone withdrawal therapy have no curative treatment options. The search for genetic, epigenetic and environmental factors involved in this malignancy really started in the early 1990s, when the first genetic map was released3, and was boosted by publication of the human genome in 20014.