Core-Biomarker Development Laboratory

Project Summary
The critical challenge in the clinical management of newly-diagnosed localized prostate cancer remains
distinguishing indolent from aggressive and life-threatening cancers. Biomarkers are urgently needed to
identify those patients who harbor aggressive disease and will derive benefit from definitive treatment. We
therefore, propose to apply complimentary proteogenomic-based discovery approaches to identify and then
validate molecular features in prostate proximal fluids and tumor tissues that will be utilized in accurate early
detection of aggressive forms of prostate cancer and improve disease risk stratification. The intended use of
these biomarkers will be the early identification of men at risk for grade progression and improved risk-
stratification for them.
We have three biomarker development laboratory aims: 1) Validate our existing urine-based biomarkers for
grade progression in a ProBE-compliant study selected from our own cohorts and the EDRN GU upgrading
study. 2) Develop and validate urine and tissue-based biomarkers for the risk-stratification of MRI “invisible”
high-grade lesions. 3) Develop and validate biomarkers to sub-stratify risk associated with deleterious
germline BRCA2 variants.
Our biomarker reference laboratory will develop and validate targeted clinically robust assays for multi-protein
biomarkers panels. We will also develop decision algorithms that are cross-referenced for statistical rigor and
benchmarked for optimal clinical performance. In addition to these BCC activities, we will develop robust
PRM-MS assays and statistically rigorous decision tools for other EDRN BCCs and CVCs.
Taken together, our EDRN biomarker characterization center will be a core part of the the EDRN ecosystem.
We will continue to actively participate in trans-Network activities, and to share patient cohorts, protocols,
datasets and analysis approaches and expertise. We will supplement these activities by focusing on
promoting the growth of new and diverse talent in biomarker development through fostering junior investigator
involvement across the full spectrum of biomarker development.

Grant Number: 5U2CCA271894-05
NIH Institute/Center: NIH
Principal Investigator: Paul Boutros