DNA Polymerase Zeta Inactivation in Prostate Cancer

Not all prostate cancer patients respond in the same way to therapies. For example, some cancers respond well to hormone therapies, and others to radiation therapy. A major reason for these differences is that different genetic changes underlie individual cancers. In order to personalize therapy and make it much more effective, it is important to take advantage of genetic analyses and determine, as early as possible during treatment, the therapeutic strategies that will be most effective to cure or control the cancer. Although it is the most common cancer in American men, more than a quarter of primary prostate cancers of both good and poor clinical prognosis are driven by unknown molecular changes in the genome. Recently, in the course of our studies of DNA repair, we analyzed prostate cancer genome data and discovered that the gene for an important DNA repair enzyme called DNA polymerase zeta (abbreviated pol zeta) is deleted in 13 percent of primary prostate cancers. This is very significant because identification of cancers with deletion of the pol zeta gene is highly likely to be useful in diagnosis and therapy. This is because suppressing pol zeta sensitizes cells to DNA damage. The absence of pol zeta is likely very important for improving therapy in these cancers, but it has never been investigated.