A new blood test could help doctors detect pancreatic cancer earlier, potentially improving survival rates for one of the deadliest cancers.
Researchers at Oregon Health & Science University have developed a test called PAC-MANN, the abbreviation for "protease activity-based assay using a magnetic nanosensor," which uses a small blood sample to detect changes in protease activity — a key indicator of pancreatic ductal adenocarcinoma, or PDAC, the most common and deadly form of pancreatic cancer.
Pancreatic cancer is often diagnosed at an advanced stage, when treatment options are limited. Current tests, such as carbohydrate antigen 19-9, or CA 19-9, are good at indicating prognosis, but aren't sensitive enough for early-stage detection. The new PAC-MANN test fills this gap by identifying signs of cancer-related activity in the blood, helping catch cancers earlier.
"The problem with pancreatic cancer is that we often catch it too late," said Jared Fischer, Ph.D., a scientist with the OHSU Knight Cancer Institute's Cancer Early Detection Advanced Research Center, or CEDAR.
"Our goal with PAC-MANN is to give clinicians a tool that can detect the disease much earlier, when more treatment options are available and there is a better chance of survival."
Fischer, an assistant professor of molecular and medical genetics in the OHSU School of Medicine, is the corresponding author of the new study detailing their new test, published today in the journal Science Translational Medicine.
The study's lead author, Jose L. Montoya Mira, Ph.D., is a research engineer at OHSU's CEDAR. An engineer and biologist by training, he joined the collaborative team to bring his extensive knowledge to create a more cost-effective, high-throughput test that could be used anywhere, not just at specialty labs or large medical universities.
"Our test could be used for people at high risk of pancreatic cancer, which is not targeted by current tests," he said. "It allows for a more robust and less invasive screening, unlike an endoscopic ultrasound and other liquid biopsy tests that require large volumes of blood, thus allowing our test to be performed more frequently for earlier detection."
Quick, accessible, accurate screening
The researchers created a non-invasive test using blood samples from 350 patients from OHSU's Brenden-Colson Center for Pancreatic Care and CEDAR; they either had pancreatic cancer, were at high risk for cancer or were controls. The research team looked for certain proteins, specifically proteases, in the blood that become more active in people with PDAC. By identifying these proteins, they developed a test that could specifically detect pancreatic cancer.
The PAC-MANN test was able to correctly distinguish patients with pancreatic cancer from healthy patients and those with non-cancerous pancreatic issues 98% of the time. It also helped spot early-stage cancer with 85% accuracy when used along with the CA 19-9 test.
Their findings also showed that PAC-MANN could track how well treatments were working. After surgery, researchers observed a decrease in protease activity, suggesting the test may help monitor whether treatments are effective.
"This test isn't just about detection — it could also help us measure how well treatments are working and guide therapeutic options," Fischer said.
"If we can track a patient's response to therapy in real-time, we can make better treatment decisions and improve outcomes."
Unlike traditional tests, PAC-MANN requires only a tiny blood sample and provides a simple fluorescent readout, making it a quick and accessible option for screening.
"The big difference with this test is the cost: It takes only 8 microliters of blood and 45 minutes to run the test at a cost of less than a penny per sample," Montoya said. "This could easily be used in rural and underserved settings, where traditional tests are not or cannot be used."
Montoya and Fischer have plans for more trials, specifically an investigator-initiated trial in collaboration with the OHSU Knight Cancer Institute and CEDAR in patients at high risk of developing pancreatic cancer.
If further validated in clinical trials, PAC-MANN could become a valuable tool for catching pancreatic cancer sooner, giving patients more treatment options and a better chance at survival.
"Hopefully," Fischer said, "this is one step toward ending cancer as we know it."
In addition to Fischer and Montoya, OHSU co-authors include: Arnaud Quentel, M.S., Ranish Patel, M.D., Dove Keith, Ph.D., Megan Sousa, B.S., Jessica Minnier, Ph.D., Benjamin Kingston, Ph.D., Larry David, Ph.D., Sadik Esener, Ph.D., Rosalie Sears, Ph.D., Charles Lopez, M.D., Ph.D., Brett Sheppard, M.D., Melissa Wong, Ph.D., and Utkan Demirci, Ph.D., with Stanford University School of Medicine.
This study was supported by CEDAR grant Full7200120, ManscriptPrep2022-1639 and Full2023-1733 and by National Cancer Institute of the National Institutes of Health Award number P30CA069533. The researchers would like to thank the Brenden-Colson Center for Pancreatic Care and Oregon Pancreatic Tissue Registry for PDAC samples, the CEDAR repository for non-PDAC samples, and S. Drennan, E. C. Manalo, T. Waugh, E. Skora, and T. Sutton for technical assistance. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
In our interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU.
With regard to this research, OHSU's Montoya and Fischer have filed a patent application for the PAC-MANN assay, #PCT/US2024/050724, "Protease Activity Sensing Probes for Detection and Prognosis of Cancer." Review details of OHSU's conflict of interest program to find out more about how we manage these business relationships.
