New research reveals clues about what goes wrong inside the pancreas years before a tumor develops
- Pancreatic cancer may begin developing years before a tumor forms
- Two protective enzymes play a role in preventing precancerous changes
- Researchers hope to discover biomarkers that can identify people at higher risk
Pancreatic cancer is one of the most difficult cancers to detect early. No one test can effectively screen for the disease and in many cases, the disease doesn't cause noticeable symptoms until it has already reached an advanced stage. That's why researchers are increasingly focused on understanding what happens in the pancreas before cancer develops.
A new study published in Nature Metabolism and led by researchers, including Roswell Park Comprehensive Cancer Center's Megan Radyk, PhD, is helping answer that question. The research uncovered important changes inside pancreatic cells that may contribute to the formation of precancerous lesions — the abnormal growths that can sometimes develop into cancer.
The findings could one day help doctors identify people at higher risk for pancreatic cancer and develop new ways to prevent the disease before it begins.
Why this research matters
Most cancer research focuses on tumors that have already formed. But scientists are learning that some of the most important opportunities to stop cancer may come much earlier.
Dr. Radyk's research focuses on the precancer stage — the period when cells first begin changing but have not yet become cancer. "Precancer and established cancers look and behave very differently," says Dr. Radyk. "My research interest lies in figuring out what goes wrong in cells years before a tumor develops and how we might stop those changes."
This is especially important for pancreatic cancer because there are currently very few ways to detect the disease early. As a result, many patients are diagnosed when treatment options are more limited.
By learning what happens inside pancreatic cells during the earliest stages of disease, researchers hope to find biological warning signs, known as biomarkers, that indicate increased risk of cancer. Those discoveries could eventually lead to earlier diagnosis, better screening tools and even new prevention strategies.
How does it work?
The study focused on two enzymes — proteins that help cells carry out essential functions. These enzymes, called G6PD and ME1, produce a molecule known as NADPH, which is needed for many biochemical reactions to keep cells active. Some of those reactions are part of the cell’s cleanup and protection system that helps cells to manage harmful molecules called reactive oxygen species (ROS). These ROS molecules are a normal byproduct of cell activity, but when too many build up, they can damage cells and contribute to disease.
The researchers used preclinical models to examine what happened to pancreas cells when G6PD and ME1 enzymes were lost or not working properly. They found that problems in these enzymes led to lower levels of NADPH. Without enough NADPH, cells were less able to clean up the harmful ROS molecules. As ROS levels increased, so did the number of precancerous lesions in the pancreas.
In simple terms, the loss of these protective enzymes made it easier for precancerous changes to develop. It's estimated that more than 400 million people worldwide have G6PD deficiency, making it one of the most common enzyme deficiencies. It's linked to an inherited genetic disorder and most people don't have any symptoms.
The researchers also found that G6PD and ME1 may play different roles as disease progresses. While reduced activity of either enzyme led to more precancerous lesions, the lesions did not always develop into cancer in the same way.
One particularly encouraging finding was that precancerous lesions could be prevented when antioxidants were added. Antioxidants help neutralize harmful molecules like ROS, suggesting that reducing cell damage may be one way to interrupt the earliest stages of disease.
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What this means for patients
For patients, the biggest takeaway is that researchers are moving closer to understanding the earliest warning signs of pancreatic cancer. The metabolic changes identified in this study could eventually lead to biomarkers that help doctors identify high-risk individuals before cancer develops.
The findings may also open the door to new prevention strategies. If scientists can pinpoint the cellular changes that occur before cancer forms, they may be able to develop treatments — or possibly dietary or lifestyle approaches — that help stop those changes from progressing.
Most importantly, the study highlights a growing shift in cancer research: stopping cancer before it starts. For a disease as challenging as pancreatic cancer, that approach could make a meaningful difference in the future.
Every new discovery about the earliest stages of pancreatic cancer brings researchers one step closer to finding better ways to detect, prevent and treat the disease — and ultimately improve outcomes for patients and families.
