Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that is usually asymptomatic at an early stage. In addition, metastases can be present even when the cancer size is relatively small. Most PDAC patients succumb within 6 months of diagnosis with only 12% of patients surviving more than five years. Clinical assays that can assist detection of incipient and early PDAC when effective treatment is possible would improve the survival rate and change the grim outlook of this disease. Unfortunately, CA19-9, the current blood-based clinical biomarker for PDAC, does not provide the accuracy needed for diagnosis, even in high-risk groups of patients. The demands on an effective biomarker for PDAC detection are considerably high compared to many other cancer biomarkers, because while the disease is less common, it is more deadly. Mass spectrometry (MS)-based methods have increasingly been emerging for clinical diagnosis, representing a technology ripe for cancer biomarker detection in clinical settings. We have previously developed a MS-based proteomic assay that significantly outperforms CA19-9 for PDAC blood detection. In this study, we aim to further validate this existing assay for PDAC blood detection through collaborative, multi-discipline efforts. Our team will conduct in-depth analytical and clinical validations to: 1) determine the performance characteristics and robustness of the assay in the context of clinical utilization; 2) refine the assay accuracy and thresholds for PDAC detection using well-annotated case-control cohorts from multiple centers; and 3) evaluate the efficacy of the assay for early detection of PDAC using pre-diagnostic cohort. The development of this proteomic assay will provide a non-invasive and affordable blood test to assist current work-up for PDAC detection in high-risk populations. This study is well-aligned with NCI’s Special Interest in analytical and clinical validation of assays for early detection of cancer using existing cohorts and prospective study designs.

Detection of pancreatic cancer at early stages (when curable treatments are effective) could represent an effective strategy to improve the survival rate of pancreatic cancer. Our prior studies have established blood- based proteomic assays that showed high accuracy in detecting pancreatic cancer from healthy and benign disease controls in multiple independent cohorts. The current proposal will carry out analytical and clinical validations of the proteomic assays, which could be potentially deployed for clinical utilities if successfully validated.