Enhancement of Radiation Therapy in Prostate Cancer by DNA-PKcs Inhibitor

Abstract : Prostate cancer (PCa) is the second leading cause of cancer death (30,000/year) in men in the USA. Surgery and radiotherapy are the most effective therapies to treat PCa patients. However, both these forms of treatment, show significant tumor recurrence with locally aggressive disease, metastasis and the morbidity in patients. Several biological disorders are thought to underlie the cause of prostate cancer. One such factor is a tumor suppressor gene DAB2IP which encodes a member of the Ras-GAP protein family. Genome wide Single Nucleotide Polymorphism (SNP) association studies in a large number of patients indicated that DAB2IP is linked with the risk of aggressive prostate cancer. DAB2IP deficient PCa cells are resistant to radiation treatment. Therefore, to improve radiation killing of these aggressive PCa cells, this proposal will explore the radiosensitizing property of NU7441, a specific kinase inhibitor of DNA-PKcs.