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Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

Abstract : The Purpose of this proposal is to exploit a molecular correlate of the Gleason grading system for prostate carcinoma in order to: a) develop improved outcome predictors; and b) identify therapeutic strategies. During this project period we have evaluated 37 prostate cancer antigens by Western blot and tissue-based assays and identified 15 with detectable levels in the plasma. Serum levels of osteopontin discriminated men with highly advanced cancer. Tissue levels of MAOA associated with relapse after prostatectomy. We determined that major challenge for the evaluation of all candidate outcome-associated proteins centers on the lack of antibodies with suitable performance characteristics of specificity and sensitivity. This limitation impacts both tissue (IHC) and ELISA-based studies of protein localization and quantitation. Newer technologies for protein quantitation such as SISCAPA and MRM may address these limitations, but they require additional optimization.