A NOVEL blood test, the PAC-MANN assay, has demonstrated significant potential for the early detection of pancreatic ductal adenocarcinoma (PDAC), a leading cause of cancer-related death. Early diagnosis of PDAC is critical, as patients are often diagnosed at advanced stages when treatment options are limited. This breakthrough could expand therapeutic opportunities and improve survival outcomes for patients with PDAC.
The study developed a noninvasive detection method based on serum protease activity, leveraging the increased protease activity in the peripheral blood of patients with PDAC. Researchers screened a series of protease-cleavable peptide probes to distinguish PDAC samples from healthy controls and noncancerous pancreatic disease. A single MMP-sensitive probe was identified, achieving 79 ± 6% accuracy in differentiating PDAC from controls. This probe was further refined into the PAC-MANN assay, a rapid magnetic nanosensor test that measures serum protease cleavage using a simple fluorescent readout. In a longitudinal cohort of patients undergoing tumour removal, the probe cleavage signal decreased by 16±24% post-surgery. In a blinded retrospective study, the PAC-MANN assay demonstrated 98% specificity and 73% sensitivity across all PDAC stages, accurately distinguishing 100% of patients with noncancer pancreatic disease from those with PDAC. When combined with the clinical biomarker CA 19-9, the assay achieved 85% sensitivity and 96% specificity for stage I PDAC detection.
These findings highlight the PAC-MANN assay as a rapid, high-throughput method requiring minimal blood volume, with the potential to significantly enhance early PDAC detection, particularly in high-risk individuals. Future research should focus on validating these results in larger, diverse populations and integrating the assay into routine clinical practice. This could transform pancreatic cancer screening, enabling earlier intervention and improving patient outcomes. Clinicians should consider the PAC-MANN assay as a promising tool for early diagnosis, particularly in patients with symptoms or risk factors for PDAC.
Katheeja Imani, EMJ
Reference
Montoya et al. Early detection of pancreatic cancer by a high-throughput protease-activated nanosensor assay. Sci Transl Med;17(785):eadq3110.
