Two drugs reverse inhibit pancreatic cancer progression

Pancreatic cancer's stealth-like nature has the attention of University of Florida scientists, who have discovered a way to reverse a key cellular process involved in its progression. UF researchers identified two small molecules that inhibit precancerous cell progression. The molecules also reversed a process known as acinar ductal metaplasia, or ADM, which precedes pancreatic cancer.

According to the National Cancer Institute, more than 60,000 Americans will be diagnosed with pancreatic cancer this year, and only about 1 in 10 of those diagnosed will survive the next five years. ADM often occurs when inflammation is present. It is a defense mechanism to avoid having the pancreas make too many digestive enzymes and destroy itself. During ADM, stable, enzyme-making acinar cells turn into protective ductal cells that line the pancreatic duct. If certain genes mutate during the transition, then the cells can become precancerous and eventually develop into cancer.

To study ADM, UF scientists built a laboratory model using animal cells with pancreatic cancer and tissue from a healthy human. They introduced the cells to two compounds — one of which was developed by Chenglong Li, Ph.D., the Nicholas Bodor Professor in Drug Discovery in the UF College of Pharmacy. The ductal cells responded by changing back to acinar cells. Pancreatic cancer can be prevented when acinar cells are maintained in their natural state.

"The findings are significant because we have now demonstrated that ADM can be reversed using drugs," said Schmittgen, who also serves as the V. Ravi Chandran Professor of Pharmaceutical Sciences in the UF College of Pharmacy. "This research may lead to developing treatments for patients who are at a high risk for pancreatic cancer development."

Reference:

Tom Schmittgen et al,Pharmacological inhibition and reversal of pancreatic acinar ductal metaplasia,Cell Death Discovery,DOI:10.1038/s41420-022-01165-4