Their study, which was published in the science journal Nature, shows a protein present on cancer exosomes was found in the blood of pancreatic cancer patients, but not in the blood of those who don’t have the disease or who have chronic pancreatitis. The findings could lead to an accurate, noninvasive diagnostic and screening tool to detect the deadly cancer, which often is only diagnosed in the later stages after metastasis has occurred.
Close to 50,000 people are diagnosed with pancreatic cancer in the United States each year, and almost 41,000 deaths are caused by the disease annually. The average five-year survival rate is 7.2%.
Exosomes are tiny, virus-sized particles released by cancer cells and contain DNA, RNA and proteins. Scientists isolated and monitored the circulating exosomes (crExos) enriched with the glypican-1 (GPC1) protein — called GPC1+ crExos — from pancreatic cancer patients’ blood.
“GPC1+ crExos were detected in small amounts of serum from about 250 pancreatic cancer patients with absolute specificity and sensitivity. It importantly distinguished patients with chronic pancreatitis from those with early- and late-stage pancreatic cancer,” said Raghu Kalluri, M.D., Ph.D., chair of Cancer Biology.
The study also found that the levels of the exosomes were significantly lower in patients following surgery to remove the tumors. Circulating exosomes from healthy donors and breast and pancreatic cancer patients were examined, and elevated levels of the GPC1+ exosomes were seen in both cancers.
“GPC1+ crExos can be detected and isolated in blood samples that were stored in freezers almost 30 years ago, unlike circulating tumor cells, which require large amounts of fresh blood,” said Kalluri. “DNA, RNA and proteins can be isolated from cancer exosomes taken from a stored specimen for further genetic and biological analyses. Therefore, cancer exosomes aren’t just a biomarker. Isolating them provides a trove of cancer-specific information.”
That information could be used to help physicians choose the best treatment for particular cancers, as well as show the effectiveness of treatments.
These markers appear to be a more reliable screening tool than the commonly used CA 19-9 biomarker, which results in many false negatives and false positives.
The study showed that the presence of GPC1+ exosomes predicted pancreatic cancer 100% of the time. And GPC1+ crExos detected the possibility of pancreatic cancer in mouse models of pancreatic cancer at a time when the mice showed no signs of pancreatic disease by MRI.
“Routine screening of the general population for pancreatic cancer using MRIs or CTs would be prohibitively expensive with the likelihood for many false positives,” said David Piwnica-Worms, M.D., Ph.D., chair of Cancer Systems Imaging. “Our study suggests the potential for GPC1+ crExos as a detection and monitoring tool for pancreatic cancer combined with imaging, with an emphasis on its application in early detection.”
If detected early, surgery involving a pancreatico-duodenectomy or the Whipple procedure can be a cure for pancreatic cancer patients. Since pancreatic cancer is often diagnosed after the disease has spread, only about 15% of patients qualify for the surgery.
“Studies comparing stage of disease with outcome following surgery suggest that death rates for pancreatic cancer would be reduced if the disease were diagnosed at an earlier stage,” said Kalluri. “This presents an unprecedented opportunity for informative early detection of pancreatic cancer and in designing potential curative surgical options.”