A new test called PAC-MANN, being researched at Oregon Health & Science University (OHSU), is hoping to take a bite out of the time and costs of detecting pancreatic cancer. The study published February 12, 2025 in the journal Science Translational Medicine notes that “pancreatic ductal adenocarcinoma (PDAC) is among the top causes of cancer-related death. Patients are frequently diagnosed in the more advanced stages when effective treatment options are limited.”
The name PAC-MANN is an abbreviation of “protease activity-based assay using a magnetic nanosensor.” The test uses a small blood sample to detect changes in the activity of a type of protein called protease, which is a key indicator of PDAC.
Jared Fischer, PhD, corresponding author of the study and assistant professor of molecular and medical genetics at the OHSU School of Medicine, said, “We concentrated on pancreatic cancer for multiple reasons. It is extremely deadly when it’s caught late, and it’s almost always caught late. There are no tests currently that are approved for early detection.”
Jose Luis Montoya Mira, PhD, the study’s lead author and a research engineer at OHSU’s Cancer Early Detection Advanced Research Center (CEDAR), is a biochemist by training. His insight into the links between biology, technology, and engineering was integral in redefining the goals of earlier tests and changing how the proteases were measured. He explained, “We wanted the test to be fast, cheap, and accurate and to have all the metrics.”
The resulting test checks all those boxes. PAC-MANN can detect the presence of pancreatic cancer with an 8 microliter blood sample in 45 minutes and provides a simple, quick, and accessible fluorescent readout.
Current Tests for Prognosis
Currently, one of the tests for pancreatic cancer is called carbohydrate antigen 19-9 (CA 19-9). The test is approved only for prognosis, when the disease has already been diagnosed, but not for detection. Dr. Fischer notes some possible drawbacks: “CA-19-9 does get lowered with treatment. But people with pancreatitis and other inflammatory diseases can have high levels of CA-19-9. Also, 10% to 20% of the entire population does not express CA 19-9, so they will never be high, which is also a problem.”
Endoscopic ultrasound is another detection method. “Basically pancreatic cancer is almost always caught incidentally when you are imaging around the pancreas for some other kind of problem, like in the GI tract,” Dr. Fischer said. “The good thing about endodscopic ultrasound is that a biopsy can be taken during the test. Those tests are necessary later, but there needs to be a test that ‘gets you in the ball park’ first before you start to do these more expensive, more invasive tests.”
PAC-MANN Early Detection and Tracking
The PAC-MANN will be useful in detecting pancreatic cancer in a range of people; for example, patients who are at high risk for the disease. Dr. Montoya Mira noted, “If you have pancreatitis, inflammatory disease of the pancreas, or diabetes, your chances of pancreatic cancer increases dramatically compared to the general population.” Patients such as those would be able to take the low-cost test at certain intervals and see if the results change over time. Other people who have certain symptoms can take the test to determine whether cancer is present.
The PAC-MANN test can detect pancreatic cancer as early as Stage 1 and continues to be “high performing” at all of the stages. During testing, it was able to correctly distinguish patients with pancreatic cancer from healthy patients and those with non-cancerous pancreatic issues 98% of the time, and it helped spot early-stage cancer with 85% accuracy when used along with the CA 19-9 test.
Dr. Montoya Mira said that the test also can guide doctors in determining treatment effectiveness. The level of protease correlates with the tumor burden, and so the clinician can see if treatment is working or not and help to guide the patient’s future therapeutic options. He said, “Clinicians don’t have a lot of tools to be able to dictate when to switch treatment or change the dose. With this test, the patient’s progress can be tracked over the course of treatment.”
Low Cost and Quick Turnaround
This possibly groundbreaking test is expected to be very low cost compared to other testing methods. Dr. Fischer noted, “Right now, our reagents cost 1 cent, but in most other tests, the reagent could be like $100.” Of course, there will be additional costs for business issues, other materials, and labor to produce the final approved test, so the actual cost is not yet available.
The test is also time-efficient, taking about 45 minutes each to run. Dr. Fischer described, “When Jose and I did it for this study, we ran 300 samples in a day, just the two of us.” He said that after approval, at first, the tests would be run in a lab, but hopefully in the future, methods may be expanded to be able to be run at the doctor’s office to improve accessibility.
Awaiting Trials
It will be some time before the PAC-MANN test is approved. Fischer notes that they are about one year from starting an investigator-initiated trial in collaboration with the OHSU Knight Cancer Institute and CEDAR in patients at high risk of developing pancreatic cancer. After that trial shows promise, the researchers can move into multi-center outreach. “Tests for pancreatic cancer can be expensive and painful,” said Dr. Fischer. We are going to do everything we can to get through the trials and get the PAC-MANN assay to the people, but unfortunately science takes time.”
The researchers are grateful to the Brenden-Colson Center for Pancreatic Care and the Oregon Pancreatic Tissue Registry “which help to get the samples that we need to analyze,” as well as the CEDAR repository for non-PDAC samples.
Dr. Montoya Mira sums up, “We want to help people. We are invested in this, and we work on this cause to improve quality of life through early detection and treatment, if possible.”
