Both drugs reversed a key step in pancreatic cancer in the lab

Pancreatic cancer often lurks in
a silent disease.
In the absence of known symptoms, it can develop and spread to other organs
undetected.

According to the National Cancer Institute, more than 60,000 Americans will be diagnosed with pancreatic cancer this year, and only one in ten of them will survive the next five years
.
In the United States, the disease is the third leading cause of cancer death because it is rarely detected
in the early stages when treatment options are most effective.

The hidden nature of pancreatic cancer caught the attention of scientists at the University of Florida, who discovered a way to
reverse a key cellular process in its development.

Researchers at the University of Florida have identified two small molecules
that inhibit the progression of precancerous cells.
The molecules also reverse a process called acinar ductal metaplasia (ADM), a precursor
to pancreatic cancer.

"To our knowledge, this is the first time researchers have been able to pharmacologically reverse ADM," said
Tom Schmittgen, Ph.
D.
, senior author of the study and chair of the Department of Pharmacy at the University of Florida College of Pharmacy, part of the University of Florida Health Center.
"With these compounds, we have the potential to treat pancreatic cancer patients early in the disease and hopefully improve existing treatment options
.
"

ADM often occurs
when inflammation develops.
This is a defense mechanism to prevent the pancreas from producing too many digestive enzymes that destroy itself
.
During ADM, stable, enzyme-making acinar cells transform into duct cells
that protect the pancreatic duct.
If certain genes are mutated during the transition, those cells become precancerous cells and eventually develop into cancer
.

To study ADM, scientists at the University of Florida built a laboratory model
using animal cells from pancreatic cancer and tissue from healthy people.
They introduced the cells into two compounds, one of which was developed
by Dr.
Chenglong Lee, the Nicholas Odor Professor of Drug Discovery at the University of Florida School of Pharmacy.
The response of ductal cells is to change back into acinar cells
.
When acinar cells remain in their natural state, pancreatic cancer
can be prevented.

"These findings are significant because we have now demonstrated that ADM can be reversed by drugs," said Schmittgen, who is also a member of the University of Florida College of Pharmacy and a member of the School of Pharmacy.
Professor
Ravi Chandran.
"This research may lead to the development of treatments
for patients at high risk of developing pancreatic cancer.
"

Schmittgen hopes the discovery will encourage scientists to think about new ways
to treat pancreatic cancer by manipulating ADM.
Future research will include testing other compounds in collaboration with Dr.
Hendrik Luesch, a co-author of the study, professor and chair of medicinal chemistry and Debbie and Sylvia DeSantis Chair in
Natural Product Drug Discovery and Development at the University of Florida School of Pharmacy.
These compounds may prove more effective because scientists are looking for new treatments for a disease with few
treatments.