We have proposed that Akt/mTOR signaling mediates cell survival and contributes to radioresistance. We intend to investigate the cellular and molecular mechanism by which inhibition of Akt/mTOR or overexpression of PTEN in both prostate cancer and its vasculature results in radiosensitization. In addition we propose to determine possible association between level or activity of these molecules and clinical response to radiotherapy. We have found differences in how irradiation affects Akt/mTOR signaling and in efficacy toward prostate cancer cells when radiation and mTOR inhibitors are combined. We found alternative death mechanisms such as autophagy are important in determining radiation sensitivity of prostate cancer cells. Furthermore we found inhibition of caspases improves radiation efficacy upon vasculature and prostate cancer cells by induction of autophagy. We plan to investigate small molecule compounds targeting these pathways for radiosensitization of prostate cancer.