Title Non-Invasive Biomarkers for Diagnosing Clinically Significant Prostate Cancer Project Summary/Abstract Despite the indolent natural history of many newly diagnosed prostate cancers (PC), most men still undergo primary curative therapy with associated side effects and costs, i.e. overtreatment. There is an clear need for the development and implementation of new management strategies for localized PC which would be enhanced if founded upon accurate assessments of disease status and the potential for indolent versus aggressive behavior. This proposal will test the hypothesis that biomarkers indicative of adverse PC characteristics (e.g. high Gleason pattern) can be reproducibly detected in the urine of men with PC. We further hypothesize that initial sampling of a panel of noninvasive urine biomarkers and the repeated evaluation of these markers over time will associate with the presence of significant versus insignificant cancer in the prostate, and thus can be used in informing decisions for surveillance or proceeding with definitive treatment. The- se hypotheses will be tested through specific aims designed to exploit distinct prostate cancer-associated RNAs using quantitative urine assays and a multi-institutional longitu- dinal cohort of men managed by active surveillance with attendant biospecimens, patho- logical, and clinical data. The successful completion of these aims will provide non-invasive tools for the initial and longitudinal assessment of prostate cancers in order to inform accurate treatment decisions for localized disease.
Prostate cancer is a commonly diagnosed malignancy with a wide range of clinical behaviors. We propose to develop non-invasive biomarkers capable of distinguishing in- significant from significant prostate cancer in order to identify those men who may avoid or delay the burden of immediate treatment safely, while concurrently identify men who may benefit from early treatment.
|Grasso, C S; Cani, A K; Hovelson, D H et al. (2015) Integrative molecular profiling of routine clinical prostate cancer specimens. Ann Oncol 26:1110-8|
|Huber, Roland M; Lucas, Jared M; Gomez-Sarosi, Luis A et al. (2015) DNA damage induces GDNF secretion in the tumor microenvironment with paracrine effects promoting prostate cancer treatment resistance. Oncotarget 6:2134-47|
|Hovelson, Daniel H; McDaniel, Andrew S; Cani, Andi K et al. (2015) Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in solid tumors. Neoplasia 17:385-99|