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Pancreatic cancer: Why it’s such a deadly disease
The 5-year survival rate for pancreatic cancer is only 7%.
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Researchers at the University of Michigan’s Rogel and Blondy Pancreatic Cancer Center are believed to be the first in the world to study the pancreases of organ donors, giving unique insight into the triggers of one of the world’s deadliest cancers.
The hope is the research will lead to new discoveries into the causes of pancreatic cancer and could help develop a way to detect the disease earlier, when it is more treatable, said Dr. Timothy Frankel, the Maud T. Lane professor of surgical oncology and codirector of the center.
There is currently no routine screening test for pancreatic cancer and no single way to diagnose the disease, which affects as many as 1 in 56 men and 1 in 60 women, according to the American Cancer Society.
It is notoriously insidious because it often shows no symptoms until a person has advanced-stage disease. By then, the options for treatment are limited.
“About 85% of patients are diagnosed with disease that has either spread to other organs or to lymph nodes,” Frankel said. “The only curative option at this point is surgery, which is reserved for those patients that have not had cancer spread beyond the pancreas or lymph nodes.
“The five-year survival rate is still dismal at 13%, which is higher than it was before, but still nowhere near where we want it to be.”
Pancreatic cancer took the life of Detroit’s beloved Queen of Soul Aretha Franklin along with “Jeopardy!” host Alex Trebek, U.S. Supreme Court Justice Ruth Bader Ginsberg, Apple CEO Steve Jobs, actor Patrick Swayze, and opera great Luciano Pavarotti.
In Frankel’s work as a pancreas surgeon, he considered whether procuring donated pancreases, and keeping them properly cooled and supplied with blood, might be a way to truly see how the cells of healthy organs work, and compare them for the first time with cells from a pancreas riddled with cancer.
“In the past, we and others relied on autopsy samples to study … non-diseased pancreases, but there’s a fundamental problem with that approach in that the pancreas is a digestive organ,” Frankel said. “Its goal is to make digestive enzymes, and the minute its blood supply is removed in a warm setting, it starts to digest itself.
“All of the building blocks and the genetic codes and all of the things that we sort of rely on to know what is driving normal processes almost instantly degrade.”
Doctors have not been able to biopsy pancreatic tissue from healthy, living patients, either, because it is too risky, Frankel said.
“There’s really no reason to ever biopsy a normal pancreas,” he said. “Unlike other parts of the GI (gastrointestinal) tract, like the stomach or colon, where biopsies are done relatively safely and routinely, you can’t biopsy the normal pancreas because of the risk of developing life-threatening pancreatic injury.”
To find out whether his idea of using donated pancreases in research would even be possible, Frankel and his colleague, Marina Pasca di Magliano, reached out to Gift of Life Michigan, which is Michigan’s only federally designated organ and tissue recovery program, to ask whether it might consider a collaboration.
That’s when they learned that “often with pancreases, a suitable recipient is not found, and donors who are really giving the ultimate gift at the end of their life also agree that if a recipient can’t be found, that they would like their tissues to be used for research to help combat disease, including cancer,” Frankel said.
The first pancreas donated to their research arrived in the lab in July 2021 and the pace slowly picked up. And now, “when pancreas donors are identified, but no recipient is found, we are then contacted and offered the pancreas, which we can then collect in a controlled, cooled manner and rapidly then bring it to the laboratory to study what’s going on in the true normal pancreas,” Frankel said.
Over the last three years, Frankel and his team him have built a biorepository of pancreas cells, tissue, proteins and genes from more than 100 donated organs from a diverse subset of Michiganders — the first of its kind in the world.
“We’ve just now sort of reached that milestone of 100 where we now have the volume and we think we can really start asking some of these deep questions,” Frankel said.
The group now has active collaborations with Johns Hopkins (University) and MD Anderson (Cancer Center) and Fox Chase (Cancer Center) to advance research into what triggers cancer cells to form in the earliest stages.
“We’re seeing an increase in young patients diagnosed with pancreatic cancer … for reasons that we don’t understand. But that is an active area of research in our group that’s actually in collaboration with MD Anderson. It is to try to understand why some young individuals get a disease that’s traditionally thought of as a disease of older individuals.”
And they’ve already made some surprising discoveries.
“The most eye-opening discovery that we made, and this happened within the first few pancreases that we received in the lab, is we started to find precancerous lesions in these pancreases,” Frankel said.
Among the first 30 pancreases they studied, more than half —18 — had lesions called pancreatic intraepithelial neoplasia, also known as PanIN.
“We did a comprehensive analysis where we actually looked at what genes were turned on in these cells compared to normal ducts, and surprisingly, we found that many of the genes turned on are some of the similar genes we see turned on in cancer, and so we really do feel like these represent sort of the earliest stages of the disease,” Frankel said.
“It was previously thought that these lesions only existed in very elderly folks, and the reason why they never progressed to cancer is because people died of other causes before these precancerous lesions could turn into cancer. But what we found was that they’re present in far more people than we would have anticipated, and in folks as young as in their 20s.
“That was a paradigm-changing finding in that we now know that it can’t be a sort of traditional progression model in which all of these eventually turn into cancer. Otherwise, pancreas cancer would be even more common.”
The discovery, he said, has spurred an entire field of research, both at U-M and beyond.
“Now, our full efforts are focused on what prevents these from eventually progressing to full cancer,” Frankel said. “Is it a failure of the protection that’s causing cancer formation and not really just a progression of the lesions themselves?
“It’s probably more than just the immune system that’s controlling these lesions from progressing. It has to be more complex than that.”
Because the pancreases are coming from organ and tissue donors, researchers also are able to get the kind of non-identifying background information about the person that might also affect their cancer risk, Frankel said, such as whether the person was a smoker or had a family history of cancer.
“We know geographic areas in which the donor lived, and so working with some of our partners here in the (U-M) Center for Healthcare Outcomes & Policy, we’re starting to now link socioeconomic and environmental hotspots with development of some of these lesions,” Frankel said.
“Being able to identify the earliest stages may get us to a point where we can find the real Holy Grail, which is an early detection test. … As a pancreatic surgeon, there are too many times when patients come in and the cancer has progressed too far and you wish you would have been able to find this six months earlier, a year earlier.
“That’s the ultimate goal.”
Contact Kristen Shamus: [email protected]. Subscribe to the Free Press.
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