With 220,000 US cases per year, prostate cancer is the most commonly diagnosed malignancy in men and the second most common cause of male cancer deaths. With the advent of effective CaP screening programs, an increasing number of men are diagnosed and treated for clinically localized or locally advanced disease and the overwhelming majority of these cases will not progress to life-threatening stages. Yet, a significant number of men will suffer disease recurrence and their early identification through predictive models constitutes a great challenge for prostate cancer therapy that requires understanding of the underlying molecular process.

The PTEN tumor suppressor pathway is among the most frequently targeted signaling cascades of human cancer. Several years ago, I discovered that the loss of a single copy of PTEN is sufficient to permit tumors to develop in animal models of cancer. We later found that complete loss of PTEN paradoxically triggers senescence, an arrested state that delays or blocks cancer development in affected cells. These findings collectively explain why many cancer biopsies only display partial loss of this tumor suppressor and establish that a non ‘Knudsonian two-hit’ mechanism of initiation is highly relevant in human cancer.