A high throughput blood-based assay for the early detection of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due in part to the cancer being diagnosed is at a late stage when effective treatment options are limited. Early detection of PDAC via liquid biopsy would revolutionize survival from the disease. To address the lack of effective non-invasive detection assays for PDAC, we developed a protease activity-based assay using a magnetic nanosensor (PAC*MANN). The PAC*MANN assay leverages protease activity in blood to amplify the signal of the target-probe based sensor. An initial screening revealed that the PAC*MANN assay could reliably differentiate patients with PDAC from healthy subjects and patients at high risk of PDAC. Finally, in two cohorts: training (n=145) and blinded validation (n=72), we demonstrated that the PAC*MANN assay had high specificity (86%) and sensitivity (78%) for detection of PDAC compared to healthy subjects. This performance was enhanced when combined with the current standard of care assay, CA19-9 (100% specificity, 84% sensitivity). Our results demonstrate a novel assay that is rapid, high-throughput, and requires low specimen volume, which may not only improve cancer detection but could be useful for monitoring of at-risk patients and could be deployed in low resource settings. One sentence summaryA high-throughput, non-invasive, rapid protease-activated nanosensor identifies pancreatic cancer from a small volume of blood