12-Lipoxygenase as a Target for Radiosensitization

DESCRIPTION (provided by applicant): The arachidonic acid (AA) lipoxygenase pathway plays an important role in tumor progression through regulating cell survival, proliferation, and angiogenesis. Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of male death in the United States. During PCa progression, it is found that the expression of 12-lipoxygenase was increased and 12-lipoxygenase may serve as a survival factor and angiogenic switch for tumor growth. In our preliminary study presented here, we found that 12-lipoxygenase may also serve as regulator for the radioresponse of PCa cells and inhibition of 12-lipoxygenase sensitizes PCa cells to ionizing radiation. We propose to target 12-lipoxygenase as an exciting avenue to develop radiosensitizer for radiation treatment of PCa. Biomide Corp has proprietary library of more than 300 synthetic compounds that were developed for inhibition of 12-lipoxygenase. The major goal of the present proposal is to evaluate these synthetic inhibitors of 12-lipoxygenase for their radiosensitizing activity. The achievement of this major goal will allow identification of novel compounds that could eventually be used as radiosensitizers for radiation treatment of PCa. The long-term objective of this project is to identify and develop clinically useful adjuvants to enhance the efficacy of radiotherapy of PCa.