Researchers zoomed in on one gene that stopped pancreatic cancer from developing in models

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Using a mouse model of pancreatic cancer, researchers have zoomed in on a single gene that stopped aggressive pancreatic cancer from developing when the scientists removed it

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One of the main drivers behind pancreatic cancer is the so-called KRAS oncogene. But new research identifies another gene whose action is crucial for the development of this cancer.

Dr. Diane Simeone, who is the director of the Pancreatic Cancer Center at the New York University Langone Health's Perlmutter Cancer Center, is the corresponding author of this new research.

Dr. Simeone and her colleagues carried out a study in mice and human patient samples to examine the role of a gene called "ataxia-telangiectasia group D complementing" (ATDC) in pancreatic tumor formation.

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Acinar cells, explain the researchers, can become cancerous when they acquire DNA mutations, including those that characterize the KRAS oncogene.

More specifically, when stressed, acinar cells can transform into what is called "acinar-to-ductal metaplasia" (ADM) — an intermediary stage that leads up to primitive, high-growth cell types.

These cells can further transform into a second stage called "pancreatic intraepithelial neoplasia" (PanIN), in which cells multiply more than they should.

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Dr. Simeone and colleagues found that the ATDC gene expression went up a few days after pancreatitis caused tissue damage, and it increased to the levels required for acinar cells to transform into ductal cells.

Furthermore, when the ATDC gene was present, in combination with the KRAS oncogene, all of the study mice developed aggressive pancreatic cancer.

However, when the researchers removed the ATDC gene, none of the cancer-prone mice developed cancer. What is more, acinar cells did not even progress to the ADM or PanIN stage.

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We found that deleting the ATDC gene in pancreatic cells resulted in one of the most profound blocks of tumor formation ever observed in a well-known mice model engineered to develop pancreatic ductal adenocarcinoma, [...] which faithfully mimics the human disease."
-Dr. Diane Simeone

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