Pancreatitis is an inflammation of the pancreas that accounts for 275,000 hospitalizations in the United States annually. Patients who suffer from hereditary pancreatitis have a 40 to 50 percent lifetime risk of developing pancreatic cancer.

The authors focused on a potentially powerful biomarker, a chemical structure created by complex sugar molecules called CA19-9, since CA19-9 is elevated in patients with pancreatitis and pancreatic cancer. Now, the team provides first evidence that CA19-9 actually causes the disease it was correlated with as a biomarker, and suggest that blocking this complex sugar structure could be used therapeutically to prevent the progression from pancreatitis to pancreatic cancer. Their findings are published in the journal Science.

Researchers investigated the properties of pancreatic cancer and zeroed in on CA19-9, a complex sugar structure that coats many proteins but had not previously been ascribed with any particular function. A single enzyme controls the final step in production of CA19-9 in humans, but this enzyme is missing in rodents. The authors generated mice that produced CA19-9, and surprisingly noted that the mice developed severe pancreatitis. The findings position CA19-9 as an attractive therapeutic target for pancreatitis.

In mice, CA19-9 recruits the immune system to repair injuries from pancreatitis. The authors found that during this recruitment process, CA19-9 can also induce a cascade of biochemical reactions propelled by the release of deleterious digestive enzymes from the pancreas. This cascade opens a transformational gateway for cancer to develop and the authors also demonstrated that CA19-9 can dramatically accelerate the growth of pancreatic tumors.

"Pancreatitis is required for developing pancreatic cancer, and we might be able to prevent that transition in patients with pancreatitis by targeting CA19-9," posited the author. "By targeting CA19-9 with antibodies in animal models, we were able to reduce the severity of pancreatitis and even prevent it from occurring."

https://science.sciencemag.org/content/364/6446/1156