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

Abstract

AbstractPancreatic 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 aproteaseactivity-based assay using amagneticnanosensor (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