Inactivation of gadd45a Sensitizes Epithelial Cancer Cells to Ionizing Radiation In vivo Resulting in Prolonged Survival

Ionizing Radiation (IR) therapy is one of the most commonly used treatments for cancer patients. The responses of tumor cells to IR are often tissue specific and depend on pathway aberrations present in the tumor. Identifying molecules and mechanisms that sensitize tumor cells to IR provides new potential therapeutic strategies for cancer treatment. In this study, we used two genetically engineered mouse (GEM) carcinoma models, brain choroid plexus (CPC) and prostate to test the impact of inactivating gadd45a, a DNA damage response p53 target gene, on tumor responses to IR We show that gadd45a deficiency significantly increases tumor cell death after radiation. Impact on survival was assessed in the CPC model and was extended in IR-treated mice with gadd45a deficiency compared to those expressing wild type gadd45a. These studies demonstrate a significant effect of gadd45a inactivation in sensitizing tumor cells to IR, implicating gadd45a as a potential drug target in radiotherapy management