Pancreatic cancer: High insulin could contribute to development

• In 2020, more than 495,000 people around the world were received a diagnosis of pancreatic cancer.
• The 5-year survival rate for pancreatic cancer is less than 10%.
• Researchers at the University of British Columbia have found a direct link between high insulin levels and pancreatic cancer via a mouse study.
• Scientists believe these findings may lay the foundations for new ways to potentially prevent and treat pancreatic cancer.

In 2020, more than 495,000 people worldwide received a diagnosis of pancreatic cancer.

This type of cancer is responsible for about 3% of all cancers and about 7% of all cancer-related deaths in the United States.

According to researchers, the only potential way of eliminating pancreatic cancer is surgery. However, only about 20% of cases are eligible for surgery at the time of diagnosis.

The 5-year survival rate for pancreatic cancer is less than 10%.

Now, a new study from researchers at the University of British Columbia has found a direct link between the high insulin levels — normally seen in people with obesity and type 2 diabetes — and pancreatic cancer via a mouse study.

Scientists believe these findings may lay the foundations for new ways to potentially prevent and treat pancreatic cancer.

The study was recently published in the journal Cell Metabolism.

High insulin levels and cancer

According to Dr. James Johnson, professor in the Department of Cellular and Physiological Sciences, interim director of the Life Sciences Institute at the University of British Columbia, he and senior corresponding author Dr. Janel Kopp — an assistant professor in the same department and Life Sciences Institute at UCB — knew there was already a well-established correlation between high insulin levels and multiple cancers.

“Pancreatic cancer has the strongest link, so Dr. Kopp and I, with our shared PhD student, Dr. Anni Zhang, started there,” Dr. Johnson told Medical News Today.

“In 2019 we showed for the first time that the high insulin found in obesity and type 2 diabetes is causal to pancreatic cancer, not just a correlation. However, we did not know how the hyperinsulinemia caused the cancer,” he noted.

“Here in the new paper, we uncover the mechanism,” added Dr. Johnson. “This is very important because pancreatic cancer is one of the most deadly cancers and it’s on the rise.”

How high insulin increases pancreatic cancer risk

For this study, Dr. Johnson and his team focused on pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer.

Researchers found that hyperinsulinemia — a condition when there is too much insulin in the body — directly contributes to pancreatic cancer initiation by increasing the production of digestive enzymes in the pancreas responsible for breaking down fat-rich foods.

When the amount of digestive enzymes increases too much, they can cause pancreatic inflammation and the development of precancerous cells.

Dr. Johnson explained:

“In the context of obesity, the excess insulin acts directly to make the pancreas cells produce more digestive juices. This ‘over-work’ stresses and inflames the pancreas causing the cells to convert to a precancerous form in the presence of a mutation in a gene called KRAS, which is common to almost all pancreatic cancers.”

Research next steps

Dr. Johnson believes higher insulin levels may also play a role in the development of other cancers.

“Our paper was co-published with a paper in Cell Reports from colleagues in Toronto, led by Dr. Vuk Stambolic, who also showed that removing the ability of breast cells to respond to high insulin significantly delayed breast cancer in the context of obesity,” he said.

“My lab is working with Dr. Liz Wellberg in Oklahoma to further explore the causality of hyperinsulinemia in breast cancer. We think insulin is important in several other cancers, too, based on the clinical correlations,” said Dr. Johnson.

Because insulin is perhaps the most actionable hormone, Dr. Johnson said they hope that showing how insulin works to initiate these cancers will improve prevention approaches.

“Our lab and our collaborators are pursuing multiple lines of research such as looking at the effects [of] high insulin on established cancer; looking at other cancers; looking for drugs that might be specific for insulin-driven cancers so that we can offer patients precision medicine; and trying to better under how to use diet as a preventative and therapeutic strategy in partnership with the Institute for Personalized Therapeutic Nutrition,” he detailed.

He also added that Dr. Kopp’s lab is working with human pancreatic tumors to learn how they respond to high insulin, high sugar, or both.

Reinforcing existing knowledge

MNT also spoke with Dr. Wael Harb, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, CA, not involved in the current research, about this study, who said his first reaction was one of cautious optimism.

“This study offers a more nuanced understanding of the interplay between hyperinsulinemia and pancreatic cancer initiation and now we know that it may be possibly specifically through the acinar insulin receptors,” Dr. Harb explained.

“It really reinforced some of the existing knowledge about the relationship between obesity, type 2 diabetes, and increased risk of cancer, especially for pancreatic cancer. So it provides a valuable understanding of the mechanism. And it could be pivotal for further studies in early detection strategy and targeted therapies,” he added.

Dr. Harb said the next step in this research should be to validate whether this is truly a causative role of hyperinsulinemia and pancreatic cancer through further studies.

“And the second is that we need to look into trying new therapies,” he noted. “Now, if this is truly what causes pancreatic cancer, can we develop treatments to prevent it or treat established pancreatic cancer?”

Ways to lower pancreatic cancer risk

Other than lowering insulin levels, we asked Dr. Harb if there were any other things a person could do to lower their pancreatic cancer risk.

“Pancreatic cancer, fortunately, is a rare cancer and we don’t understand why some people have it and some don’t,” he explained. “We know there are certain families that have familial pancreatic cancer. [And] patients with BRCA mutations have increased pancreatic cancer [risk].”

“So knowing the family history and genetic predisposition, if we have a family that has a history of pancreatic cancer […] it would be worthwhile to do genetic testing,” Dr. Harb continued. “And these patients would need to be observed more closely, so we will do imaging studies on a regular basis to monitor the pancreas.”

“Outside of that, for the average person who doesn’t have [a] family history, we would recommend generally for anyone to prevent cancer is [a] healthy lifestyle — [a] diet rich in vegetables and fruits, exercise, [and] avoiding things that can cause cancer, like smoking (and) excessive alcohol,” he added.

Source: Read Full Article