Pancreatic cancer is a killer; 85% of patients die within nine months of diagnosis. A new study sheds light on how the cancer spreads throughout the body.

The study, published in the journal Cell by researchers at Cold Spring Harbor Laboratory, reports that the cancers spread is controlled by epigeneticschanges that arent hardwired into DNA, but affect how genes are expressed. To make this discovery, scientists grew and tested balls of cells that mimic the shape and behavior of the pancreas, known as pancreatic organoids. These organoids may one day lead to personalized cancer treatments.

In a few years, pancreatic cancer will become the second-leading cause of cancer death in the United Stateseclipsing colon and breast canceraccording to Howard Crawford, director of the pancreas research program at University of Michigan. But pancreatic cancer garners far less public attention than other malignancies.

Thats because we dont have any survivors, Crawford tells GEN. We dont have people that can bring a lot of press. We all have to rely on the patients families and loved ones to raise awareness. And thats a challenge.

The cancer is so deadly because pancreatic tumors regularly break off and spread to far-flung regions of the bodya process known as metastasis. Scientists have tried to identify genes that control the cancer, but genetics dont tell the whole story.

We have a pretty good understanding of how pancreatic cells become pancreatic tumor cells, said Chang-Il Hwang, postdocoral fellow and co-first author of the study. We dont know how they metastasize to distant organs.

To understand the cancers spread, Hwang and colleagues collected pancreatic tumors and their metastases from mice and grew the cells in a dish. The cells formed tiny 3D structures known as organoids, which looked and acted like pancreatic cells.

When the researchers compared organoids from the initial tumor to organoids from the metastases, they didnt find major genetic differences. But they did see that metastatic organoids had more active enhancersshort regions of DNA that boost gene expression by binding to proteins.

The roughly 800 enhancers active in metastatic organoids were linked to embryonic pancreas formation. In effect, metastatic cells were turning back the clock and reverting to an earlier state in order to leave the pancreas.

The researchers analyzed the DNA sequences of the enhancers to find the protein that binds to them, and found FOXA1. When they expressed high levels of FOXA1 in organoids and injected them into the tails of mice, the organoids spread to the lunga sign of metastasis. But when the researchers injected mice with organoids lacking FOXA1, they didnt metastasize.

The scientists also checked human pancreatic tissue samples and found that FOXA1 increased with disease severityconsistent with its role in metastasis. Hwang is now working to better understand how FOXA1 works in order to develop future therapies.

The future goal will be to try to utilize this information to benefit metastatic pancreatic cancer patients, said Hwang.

Because organoids are grown from a patients cells, Hwang and others may be able to use them to personalize cancer treatments. A researcher could grow organoids from a tumor, treat those organoids with a variety of drugs, and see which drugs work best before administering the drug to a patient. But this takes timesomething that pancreatic cancer patients have in short supply.

It takes almost a month or more to establish a good organoid culture from a pancreatic patient, said Crawford. If a patient has six to nine months to live, thats not a lot of time.

Crawford believes the key is earlier diagnosis. Ten percent of patients have a family history of the disease and genetic markers that put them at risk. He thinks these people should be screened early and often. But screening the rest of the population will be a challenge.

We have to have a fairly perfect way to screen [the] population, he said. Even with a 98% or 99% success rate theres a large number of people there that would falsely be diagnosed and a few that would be missed.

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Pancreas in a Dish Tells Story of How Metastatic Cells Turn Back Time - Genetic Engineering & Biotechnology News (press release)