Scientists are developing tests to detect pancreatic cancer in the early stages using small blood samples.
If caught early, it could potentially treat pancreatic cancer. However, patients are not usually diagnosed until the cancer has already spread, reducing the chances of survival. The disease is projected to cause more than 51,000 deaths in the United States this year, accounting for more than 8% of the country’s total cancer deaths.
One reason pancreatic cancer is often diagnosed in advanced stages is that doctors do not take routine screening tests for the disease, but several tests have been investigated for those known to be at high risk. Now, researchers are developing a test that says they hope that just one drop of blood can diagnose fatal cancer.
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They called out Test Pac-Mann, which represents “protease activity-based assays using magnetic nanosensors,” and explained it in a paper published earlier this year in Science Translational Medicine.
The test shows some promising early results, but experts have told Live Science that they are not yet ready to use as a screening tool.
How Pac-Mann works
The classic arcade game hero, Pac-Man, chases after the ghosts, and, like Goble’s ghosts, pancreatic tumors send protease enzymes that bite the surrounding tissue. Protease enzymes break down proteins and help cancer cells enter the bloodstream, metastasize, and go beyond their original location.
Related: Simple blood tests can become the future of cancer diagnosis
However, these enzymes appear in relatively low abundances in the bloodstream, and their activity levels vary from person to person with cancer. This makes detection difficult with existing technologies.
To make these enzymes easier to detect, Pac-Mann uses small magnetic beads coated with a fluorescent “probe”. The idea is that when a drop of blood from a cancer patient is added, the tumor-made protease slices the probe from the beads and releases a fluorescent tag. A strong magnet pulls out all the beads, leaving only the released fluorescent pieces.
The remaining glow measured on a lab device called a fluorometer is a readout. The more fluorescence, the higher the protease activity, indicating the possibility of the tumor being present. The probes used in the tests specifically respond to MMP2, an enzyme identified as a standout enzyme in the blood of people with pancreatic cancer, compared to healthy people. That said, enzymes are not intrinsic to cancer, as they have other known biological functions.
“The PAC-Mann assay requires a small amount of blood,” Jared Fischer, co-author of the study at Jared Fischer, a scientist at the Center for Advanced Research at Early Detection of Cancer (CEDAR), told Live Science in an email.
Because very little blood is needed, users may use home skin stabs and microneedle devices, he said, “thus, it can remove the need for a venous blood draw and ph tax, reducing the equipment and labor required to run the test.
Put Pac-Mann in the test
The team validated the test using blood samples from 110 patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. They also examined the blood of 170 healthy people, 45 people with pancreatic inflammation (pancreatitis) and 31 people with pancreatic tumors.
They found that PAC-Mann correctly detected 73% of PDAC cases. In particular, detection of early stage PDAC was slightly lower at 62%. In this test, 98% of non-cancerous samples were correctly identified. This means that overall, 27% of PDAC cases have illegally returned to “negative” and 2% of non-cancerous samples have been mistakenly identified as cancer. These two important metrics are known as test “sensitivity” and “specificity” respectively.
The team then combined PAC-Mann with a test of CA 19-9, another substance released by pancreatic tumors. High levels of CA 19-9 can be a sign of pancreatic cancer, but other conditions can also drive CA 19-9 and are not used for standalone cancer screening.
When PAC-Mann was combined with CA 19-9 measurements, the sensitivity of the combination test increased to 87% on average, and 85% for early stage cancer. However, specificity fell slightly to 96%.
Jose Montoya Mira, co-author of the study by Jose Montoya Mira, research engineer at Cedar, hopes that Pac-Mann can be used as a screening tool for people known to be at high risk for pancreatic cancer, said in a statement. It can also be used alongside cancer treatments to see how well they are working, the authors said. CA 19-9 is an example of a test already used for this latter purpose.
However, Dr. John Neoptolemos, a researcher at the University of Heidelberg in Germany, called attention. Protease enzymes are not cancer-specific, he told Live Science via email. Enzymes play a variety of roles in the healthy body, such as supporting digestion and immunity.
“This strategy is unlikely to be used for early detection,” Neoptolemos said. “This assay is not directly specific to cancer and has less specificity of the screening.”
Neoptolemos added that artificial intelligence-based testing, which has been developed to identify and screen high-risk populations, is currently promising. So, Pac-Mann will have to show clearer value additions than these new methods, Neoptolemos said.
That said, Pac-Mann is still under development. The manufacturer is currently expanding its research focusing on high-risk groups, particularly to see if PAC-Mann can detect tumors faster than is currently possible. Montoya and Fisher have filed a patent application for PAC-Mann and are in the process of licensing the assay to the company.
This article is for informational purposes only and is not intended to provide medical advice.
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