A team of researchers have identified a gene that influences the shape of normal pancreatic cells and, as a result, could set the foundation for pancreatic cancer to develop.

The study, published in Nature Communications, suggests that targeting the gene in question – protein kinase D1 (PKD1) – could lead to new ways of halting the development of one of the most difficult tumors to treat.

“As soon as pancreatic cancer develops, it begins to spread, and PKD1 is key to both processes. Given this finding, we are busy developing a PKD1 inhibitor that we can test further,” says the study’s co-lead investigator, Dr. Peter Storz.

Pancreatic cancer is the fourth most common cause of cancer death in the US. The American Cancer Society (ACS) estimate that around 48,960 people will be diagnosed with the disease in 2015, with an estimated 40,560 people dying. At present, the lifetime risk of a person developing pancreatic cancer in the US is around 1 in 67 (1.5%).

The pancreas is an organ containing exocrine and endocrine glands. These glands produce a juice full of enzymes that aid the digestion of food as it passes through the gut. The pancreas also contains a number of endocrine cells that produce hormones such as insulin and glucagon and release them directly into the blood.

“We need a new strategy to treat, and possibly prevent, pancreatic cancer. While these are early days, understanding one of the key drivers in this aggressive cancer is a major step in the right direction,” states Dr. Storz, a cancer researcher at Mayo Clinic.

When cells in the pancreas that secrete digestive enzymes (acinar cells) turn into duct-like structures, pancreatic cancer can develop. Oncogenic signaling – that which causes the development of tumors – can influence these duct-like cells to form lesions that are a cancer risk.

Acinar cells normally morph in this manner following injury or after inflammation of the pancreas. Fortunately, the process of morphing is reversible.

Researchers demonstrate the influence of PKD1 with mouse-derived 3D model

Researchers from Mayo Clinic’s campus in Jacksonville, FL, and the University of Oslo, Norway, developed a 3D model of pancreatic cells derived from a mouse in order to test the influence of PKD1. In this model, the team could either block the gene or induce its activity and observe the effects.

A week of stimulating the expression of PKD1 led to the transformation of acinar cells into the vulnerable duct-like structures. Conversely, by blocking the gene, the researchers were able to reduce the number of duct-like cells and lesions that formed.

The 3D model has made investigating what happens within the pancreas a much simpler process, according to Dr. Storz:

“This is a great model for examining what happens in a signaling pathway – we can see the changes by simply using a microscope. This model tells us that PKD1 is essential for the initial transformation from acinar to duct-like cells, which then can become cancerous.”

Dr. Storz believes that working out how to prevent acinar cells from turning into duct-like structures could be the key to creating new effective ways of treating pancreatic cancer:

“If we can stop that transformation from happening – or perhaps reverse the process once it occurs – we may be able to block or treat cancer development and its spread,” he concludes.

Earlier this year, Medical News Today reported on a study identifying a gene called ATDC that may explain why pancreatic cancer is so aggressive.

Written by James McIntosh

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