By identifying the molecular starting point when certain cells in the pancreas become pre-cancerous lesions, researchers behind a new study believe they have opened the door to exploring ways to prevent the deadly disease.
Study leader Dr. Peter Storz, a cancer biologist at the Mayo Clinic in Jacksonville, FL, who – with colleagues – describes the findings in the journal Cancer Discovery, says:
“Pancreatic cancer develops from these lesions, so if we understand how these lesions come about, we may be able to stop the cancer train altogether.”
Dr. Storz says there is a pressing need for new treatments and ways to prevent pancreatic cancer, one of the most aggressive human cancers. The disease is the fourth leading cause of cancer death in the US.
On average, patients with pancreatic cancer face a 20% chance of living more than 1 year after diagnosis. The main reason for such a poor prospect is that symptoms do not show until the cancer is well advanced.
According to the National Cancer Institute, in 2014, over 46,400 people will be diagnosed with pancreatic cancer and over 39,500 will die of the disease.
For the study, the team investigated cells containing mutations of a gene that regulates a cell division protein. Called Kras, the gene is known to be mutated in over 95% of pancreatic cancer cases.
The researchers describe how they identified the detailed steps that Kras-mutated acinar cells follow as they change into duct-like cells with properties similar to stem cells – a type of cell often found in cancer.
They noticed that Kras proteins in the acinar cells switched on a molecule called ICAM-1. This in turn attracts macrophages – inflammatory immune cells that release a variety of proteins, including some that loosen the pancreatic cell structures. When they become looser, the acinar cells then transform into different types of cell – including the type that leads to pre-cancerous lesions.
Dr. Storz says their study shows a “direct link between Kras mutations and the inflammatory environment that drive the initiation of pancreatic cancer.”
The team also found they could halt the process in mice. They did this in two ways. One way was by depleting the macrophages, and the other way was by blocking the transforming cells with an antibody that shuts down ICAM-1.
“Doing either one reduced the number of precancerous lesions,” says Dr. Storz, noting that an antibody that blocks ICAM-1 has already been developed and is currently being tested for treating stroke, rheumatoid arthritis, and other ailments.
He also says the key to developing targeted ways to prevent and treat pancreatic cancer will be understanding “the crosstalk between acinar cells with Kras mutations and the microenvironment of those cells.”
The National Institutes of Health funded the research.
The study follows another recent report from Medical News Today about the prospect of a simple blood test for pancreatic cancer, as more potential biomarkers for the disease emerge.