Dr. Granger has been working closely with Drs. Sean Mulvihill and Matthew Firpo of the Department of Surgery and Huntsman Cancer Institute to develop an innovative diagnostics platform to improve early cancer detection and cancer risk assessment. They have approached this goal through the very sensitive quantitation of a panel of biomarkers specific for a disease. The platform is antibody-based where specially designed nanoparticles label immobilized biomarkers captured from a small volume of patient blood. Quantitation of these labels is performed with surface-enhanced Raman scattering (SERS) ? a system sensitive enough to detect a single nanoparticle. Dr. Granger explained, “This platform and the use of a panel of biomarkers will serve as the cornerstone in making earlier cancer detection and improved patient outcomes a reality.”
Pancreatic cancer was chosen as a disease model to validate the platform after an extensive survey of critical issues in human health. Dr. Granger and her collaborators have been working to create an effective biomarker panel to diagnose pancreatic cancer, stratify patients for therapeutic regimens, and monitor their response to that therapy. Pancreatic cancer exhibits traits common to most diseases that progress asymptomatically, including the unavailability of one ideal tumor marker with high clinical sensitivity and specificity.
Since development of pancreatic cancer arises from a range of causative mutations, Dr. Firpo is hopeful that a panel of multiple biomarkers with overlapping detection capabilities will likely provide improved outcomes. Currently, the ability to identify health risk, disease susceptibility, and response to therapy remains unreachable due in part to the technical inability to easily screen a single sample for the large number of biomarkers that potentially make up a “disease map”. Dr. Granger states that, “The SERS platform is designed to remove this hurdle and to do so at costs that enable routine testing for everyone.”
Drs. Mulvihill and Firpo have identified 169 possible blood-based markers of pancreatic cancer, some of which have demonstrated limited correlative value individually. Dr. Firpo commented, “The SERS platform that Jennifer is using, in concert with traditional screening methods, will enable us to identify an effective biomarker panel for this cancer”. As a starting point, two relevant biomarkers for pancreatic cancer (carbohydrate antigen 19-9 and matrix metallopeptidase 7) have been combined for a crucial proof-of-concept study. Dr. Granger emphasized, “It is exciting that we have been able to successfully detect both biomarkers out of human serum at levels below those attainable using conventional diagnostic platforms.”
Once validated, the platform will be used for marker and marker panel discovery. It is uniquely suited for rapid deployment as a cost-effective, portable, and robust system for multiplexed diagnostic assays in a clinical setting, and it will form an essential part of the personalized medicine infrastructure.
Dr. Jennifer Granger is a Research Scientist in the Center for Nanobiosensors at the University of Utah. She earned a Ph.D. in Analytical Chemistr y in 2001 and an M.S. in Organic Chemistry in 1998 from Iowa State University. Prior to joining the NanoInstitute, she directed the mass spectrometry analytical core at AstraZeneca Pharmaceuticals in Waltham, MA. Her current research interests focus on low-level detection of markers indicative of disease states.