Research: Two medications reverse critical pancreatic cancer step in lab

Only approximately 1 in 10 Americans who are diagnosed with pancreatic cancer will survive for the following five years, according to the National Cancer Institute, which predicts that more than 60,000 Americans will be affected by the disease this year. Because it is rarely found in the early stages, when treatment options are most effective, the disease ranks as the third most common cause of cancer deaths in the United States. The stealthy aspect of pancreatic cancer has caught the attention of University of Florida researchers, who have found a technique to stop a crucial biological function that contributes to its spread.

Two tiny compounds that prevent the growth of precancerous cells have been found by UF researchers. Additionally, the molecules stopped a condition called acinar ductal metaplasia, or ADM, which occurs before pancreatic cancer.

"To our knowledge, this is the first time researchers have been able to pharmacologically reverse ADM," said Tom Schmittgen, PhD, the study's senior author and chair of the department of pharmaceutics in the UF College of Pharmacy, part of UF Health, the university's academic health centre. "With these compounds, we could potentially treat a pancreatic cancer patient at an earlier stage of the disease and hopefully improve the treatment options available."

When there is inflammation, ADM frequently develops. It serves as a safeguard against the pancreas producing too many digestive enzymes and self-destructing. Stable acinar cells that produce enzymes change during ADM into protective ductal cells that line the pancreatic duct. The cells may turn precancerous and later turn into cancer if specific genes mutate during the process.

Using tissue from a healthy person and animal cells with pancreatic cancer, UF researchers created a lab model to examine ADM. One of the two chemicals they gave the cells was created by Chenglong Li, PhD, the Nicholas Bodor Professor in Drug Discovery at the University of Florida College of Pharmacy. In response, the ductal cells converted back to acinar cells. When acinar cells are kept in their native condition, pancreatic cancer can be avoided.

"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."

Schmittgen expects that this discovery may inspire researchers to consider novel ADM-based therapies for pancreatic cancer. In the future, Hendrik Luesch, PhD, a co-author of the study and professor of medicinal chemistry and holder of the Debbie and Sylvia DeSantis Chair in Natural Products Drug Discovery and Development at the University of Florida College of Pharmacy, will work with other researchers to test additional compounds. As researchers look for novel treatments for a condition with few available options, these substances might prove to be more efficient.

Published in the journal Cell Death Discovery, the study is titled "Pharmacological Inhibition and Reversal of Pancreatic Acinar Ductal Metaplasia." (ANI)