BCC for Prostate Cancer: Discovery and Translation of Biomarkers for Clinical Unmet Needs

Active surveillance (AS) is the preferred management option for low risk prostate cancer (PCa) patients who would benefit from conservative treatment. However, due to the lack of reliable methods in the initial clinical evaluation to identify true low-risk PCa patients for AS enrollment and during AS monitoring to detect a rising

risk of progression, patients who could benefit from conservative management through AS are often over-treated, yet at the same time patients initially chosen for AS with a missed high-risk disease are under-treated. The goal of the proposed EDRN Biomarker Characterization Center (BCC) is to develop and validate in vitro diagnostic

multivariate index assays (IVDMIA) that combine a panel of biomarkers into a single-valued numerical index with the intended use for the clinical unmet needs for 1) assisting in the preoperative assessment of PCa aggressiveness and decision for enrollment into AS; and 2) detecting a rising risk of progression during AS to

triage patients for additional and possibly more invasive procedures for needed disease reclassification. The objective for the IVDMIA development is to improve specificity while maintaining a high negative predictive value in order to safely enroll more patients with true low-risk PCa into AS and reduce the number of unnecessary

biopsies and or costly workup procedures for patients in AS. To achieve this goal, we propose an integrated BCC at the JHU consisting of a multi-disciplinary team including PIs from current EDRN BDL (Dr. Hui Zhang) and BRL (Dr. Daniel W. Chan), and a previous CVC (Dr. Alan Partin). The targeted population is JHU AS patients

with >20-years of enrollment and clinical follow-up. Our team has many years of experience in biomarker discovery, verification, validation, and translation into clinical diagnostics and the development of IVDMIA, e.g. OVA1, the 1st proteomics IVDMIA cleared by the FDA (2009). We plan to take advantage of the serum

biomarkers already discovered for aggressive PCa from our current BDL and BRL and begin the verification and validation in the targeted AS population by our BRL. In parallel, our BDL will focus on the discovery of new candidate serum, urine and tissue biomarkers by applying cutting edge technologies to the AS population, such

as mass spectrometry based high throughput proteomics, protein modifications, and single cell analysis of laser- capture-microdissected tissues. We plan to combine these biomarkers into IVDMIAs. Finally, we will work with our industry partners to translate these IVDMIAs into CLIA certified and/or FDA cleared/approved clinical

diagnostics. We believe with these innovative, yet, practical approaches, our BCC offers the best opportunity to make significant contributions to the EDRN network and address the critical clinical unmet needs for PCa patients. If the over-treatment, under-treatment, decrease in unnecessary biopsies, and increase in biopsy

accuracy can be successfully addressed, the morbidities associated with PCa diagnosis and treatment can be significantly decreased, while enhancing the detection and treatment of clinically significant PCa. In addition, our BRL, a CLIA and CAP certified clinical laboratory at JHU, will serve as a resource center for the EDRN network.