Nitric oxide and pancreatic cancer pathogenesis, prevention, and treatment.
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Pancreatic cancer is hallmarked by aggressive biology and extreme lethality and very high mortality rates. The underlying molecular mechanism of its rapid development and progression is unclear, however. Recent identification and functional validation of nitric oxide (NO) production in pancreatic cancer suggest a role for NO in the pathogenesis of this disease. Conceivably, overproduction of NO imposes an adverse selection pressure on the tumor microenvironment, which causes genetic and epigenetic changes in tumor and tumor stromal cells and promotes the evolution of these cells into more malignant cells conferred with a tremendous survival and growth advantage. Designing effective strategies targeting NO to control pancreatic cancer development and progression requires a full understanding of the molecular mechanisms of signaling of NO production and action in the tumor microenvironment.