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Two drugs reverse key pancreatic cancer step in the lab

Date:
October 19, 2022
Source:
University of Florida
Summary:
Two drugs -- one brand new -- reverse pancreatic cell changes that presage one of the hardest cancers to treat. Tested in cells, the drugs would be a promising early cancer treatment if they work in clinical trials.
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Pancreatic cancer often lurks as a silent disease. With no known symptoms, it can progress undetected and spread to other organs.

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. The disease ranks as the third leading cause of cancer deaths in the U.S. because it is rarely detected in the early stages when treatment options are most effective.

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.

"To our knowledge, this is the first time researchers have been able to pharmacologically reverse ADM," said Tom Schmittgen, Ph.D., 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 center. "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."

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."

Schmittgen hopes this discovery will encourage scientists to think about new ways to treat pancreatic cancer by manipulating ADM. Future research will involve testing other compounds in collaboration with Hendrik Luesch, Ph.D., a co-author of the study and a professor and chair of medicinal chemistry and the Debbie and Sylvia DeSantis Chair in Natural Products Drug Discovery and Development in the UF College of Pharmacy. These compounds may prove to be more effective, as scientists seek new treatments for a disease with very few treatment options.


Story Source:

Materials provided by University of Florida. Original written by Matthew Splett. Note: Content may be edited for style and length.


Journal Reference:

  1. Lais da Silva, Jinmai Jiang, Corey Perkins, Kalina Rosenova Atanasova, Julie K. Bray, Gamze Bulut, Ana Azevedo-Pouly, Martha Campbell-Thompson, Xiaozhi Yang, Hesamedin Hakimjavadi, Srikar Chamala, Ranjala Ratnayake, Raad Z. Gharaibeh, Chenglong Li, Hendrik Luesch, Thomas D. Schmittgen. Pharmacological inhibition and reversal of pancreatic acinar ductal metaplasia. Cell Death Discovery, 2022; 8 (1) DOI: 10.1038/s41420-022-01165-4

Cite This Page:

University of Florida. "Two drugs reverse key pancreatic cancer step in the lab." ScienceDaily. ScienceDaily, 19 October 2022. <www.sciencedaily.com/releases/2022/10/221019172134.htm>.
University of Florida. (2022, October 19). Two drugs reverse key pancreatic cancer step in the lab. ScienceDaily. Retrieved December 20, 2024 from www.sciencedaily.com/releases/2022/10/221019172134.htm
University of Florida. "Two drugs reverse key pancreatic cancer step in the lab." ScienceDaily. www.sciencedaily.com/releases/2022/10/221019172134.htm (accessed December 20, 2024).

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