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Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to radiation therapy (RT), chemotherapy, or a combination of these modalities, and surgery remains the only curative intervention for localized disease. Although cancer-associated fibroblasts (CAFs) are abundant in PDAC tumors, the effects of RT on CAFs and the response of PDAC cells to RT are unknown. Using patient samples and orthotopic PDAC biological models we showed that RT increased inducible nitric oxide synthase (iNOS) in the tumor tissues. Mechanistic in vitro studies