Novel Blood Test Enables Early Pancreatic Cancer Detection

TOPLINE:

The new blood-based assay PAC-MANN-1 (protease activity–based cancer marker using magnetic nanosensor-1) identified pancreatic ductal adenocarcinoma (PDAC) across all stages with high specificity and sensitivity. The assay showed improved detection of early-stage cancer when combined with carbohydrate antigen 19-9 (CA 19-9).

METHODOLOGY:

• CA 19-9, the only Food and Drug Administration–approved biomarker for PDAC, has a low positive predictive value for early-stage disease, highlighting the urgent need for specific, accessible, and cost-effective biomarker assays for effective screening and monitoring of cancer risk.
• Researchers aimed to detect PDAC by taking advantage of the increased cancer-associated protease activity in the blood of patients with the disease. They screened a series of protease-cleavable peptide probes for the ability to differentiate patients with PDAC from healthy individuals and those with noncancer pancreatic disease.
• They identified a matrix metalloproteinase-2 (MMP2)–sensitive probe that could distinguish patients with and without PDAC and used it to develop the PAC-MANN-1 assay for detecting PDAC by measuring serum protease cleavage with a simple fluorescent readout.
• The assay was tested in pretreatment serum samples of 110 patients with PDAC and 246 patients without PDAC. Of those without PDAC, 170 were healthy control individuals and the remainder were patients with pancreatitis or pancreatic neoplasia.
• To determine whether the probe was specific to PDAC, researchers compared longitudinal samples before and after surgical removal of primary pancreatic tumors in patients who did or did not receive neoadjuvant chemotherapy.

TAKEAWAY:

• The PAC-MANN-1 assay identified PDAC with 98% specificity and 73% sensitivity and accurately distinguished patients with chronic pancreatitis or pancreatic neoplasias from those with PDAC. In contrast, the use of CA 19-9 showed a 45% sensitivity for detecting PDAC.
• When analyzed based on cancer stage, the PAC-MANN-1 assay showed higher sensitivity than the use of CA 19-9 for stage I (62% vs 31%), stage II (56% vs 31%), stage III (92% vs 54%), and stage IV (85% vs 69%) PDAC.
• Combining the PAC-MANN-1 assay with CA 19-9 improved detection of stage I PDAC, with a sensitivity of 85% and 96% specificity.
• In the longitudinal cohort, the PAC-MANN-1 assay demonstrated a 16% reduction in protease activity signal after surgery for the removal of primary tumors compared with before surgery (P = .0003) and a 29% reduction in patients who received neoadjuvant chemotherapy before surgery (P = .016).

IN PRACTICE:

“We demonstrated that PAC-MANN-1 has promise to serve as the foundation for a sensitive, inexpensive, low serum volume and scalable early detection of PDAC assay that can be used regularly in high-risk patient populations or the general population with less access to medical tests,” the authors wrote.

SOURCE:

This study, led by Jose L. Montoya Mira, PhD, Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, Oregon, was published online in Science Translational Medicine.

LIMITATIONS:

The current PAC-MANN-1 assay might require laboratory runs as it was not designed as a point-of-care device. The assay has only been tested on venous blood draws, and its application in pharmacies, home, or rural and underserved settings will need an alternate design not requiring venous blood draws. Moreover, the assay was not tested for cancer types other than PDAC. 

DISCLOSURES:

This study was funded by grants from the Cancer Early Detection Advanced Research Center and National Cancer Institute. Two authors reported filing a patent application for the PAC-MANN assay. One author reported being a founder and having equity interest in several companies developing microfluidic tools, imaging technologies, and extracellular vesicle isolation. Another author declared being on the executive board of the Pancreatic Cancer Early Detection Consortium, serving on scientific advisory boards for a biopharmaceutical company and cancer research organizations, and sponsoring research from two pharmaceutical companies. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.