Tuesday, May 6, 2025
5/6/2025
A Prognostic Blood Test to Monitor Pancreatic Cancer Treatment by MiRNA Profiling - Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of less than 7%. The success in developing therapies for other cancers over the last two decades has not improved the dismal overall survival (OS) rate for PDAC. It is now becoming increasingly apparent that personalized medicine based on the genetics of a tumor will be essential for developing a treatment strategy. Thus, there is an urgent need to develop a noninvasive, genetic biomarker-based surrogate monitoring test to personalize therapy by rapidly assessing treatment efficacy to make early decisions on therapy strategy and to minimize the "cost of failure." Meta-analysis combining several studies shows that profiling dysregulation of a large panel of circulating microRNA (miRNA) sequences in blood will potentially have over 85% specificity and sensitivity to detect PDAC-related alteration due to therapy. For the Phase II study, 22 circulating miRNAs impacted by PDAC have been chosen to validate a blood test technology. The technology is a quantitative microarray where binding as low as 0.4 zeptomoles of target molecules to a microspot of immobilized probes will be measured at 100% specificity, zero background, 10 attomolar sensitivity, and a dynamic range of five orders of magnitude. The novel detection method, called Scanning Electrometer for Electrical Double-layer (SEED), will measure local redox on individual microarray spots (patterned on a monolith electrode) to quantify miRNA expression levels without PCR and cDNA conversion. The signal is zero for no binding (i.e., absolute). The binding is by an electrochemical redox enhanced binding (EREB) process to focus as few as 1,800 copies of target molecules to probe molecules immobilized on a Au electrode in <30 min. A linear semi-logarithmic response, similar to a standard curve of qPCR, is obtained for a target concentration ranging from 10-2 to 103 fM. Analysis on plasma from a healthy donor shows a remarkable quantitative correlation between synthetic miRNA in buffer and spiked in plasma ranging from 10 aM to 1 pM. Analysis of 5 miRNA sequences on a chip in patient plasma shows multiplexing and a quantitative correlation with qPCR. The two-year program to validate the EREB/SEED technology will be organized into three specific aims: (1) perform direct miRNA analysis using plasma from a healthy subject that will be spiked with a mixture of synthetic miRNA to evaluate the accuracy of the technology in a biospecimen; validate the technology on plasma from patient undergoing, (2) chemotherapy and (3) radiation therapy, to study the efficacy of the therapy by profiling miRNA at different time points. The validation will be based on a quantitative figure of merit.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).