Possible Metabolic Treatment for Pancreatic Cancer Would Target an Enzyme (Arginase 2) That Helps Dispose of Excess Nitrogen

Pancreatic cancer is now the third leading cause of cancer mortality. Its incidence is increasing in parallel with the population increase in obesity, and its five-year survival rate still hovers at just 8 to 9 percent. Research led by Nada Kalaany, PhD, at Boston Children's Hospital and the Broad Institute of MIT and Harvard, now suggests a novel approach to treating this deadly cancer: targeting an enzyme that tumors use to get rid of nitrogen. The study, published online on August 14, 2017 in Nature Communications, provides evidence that targeting the enzyme arginase 2 (ARG2) (image) can curb the growth of pancreatic tumors, especially in people who are obese. The open-access article is titled “Critical Role for Arginase 2 in Obesity-Associated Pancreatic Cancer." The researchers began by introducing human pancreatic tumors into obese and lean mice. They then analyzed what genes the tumors turned on and what metabolic products they were producing. They found that tumors in obese mice had enhanced expression of many genes involved in metabolizing nitrogen, a natural byproduct of cells when proteins are broken down. Until now, how nitrogen excess affects tumor growth has been largely unknown. "We found that highly malignant pancreatic tumors are very dependent on the nitrogen metabolism pathway," says Dr. Kalaany, a researcher in Boston Children's Division of Endocrinology and an Assistant Professor at Harvard Medical School.
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