Stanford Molecular and Cellular Characterization Laboratory

NCI U01 - Principal Investigator: James Brooks, MD

Nearly all prostate cancers are detected by screening with serum Prostate Specific Antigen (PSA). Unfortunately, aggressive screening over the last 25 years has led to detection of many small, early stage prostate lesions not destined to progress or kill men. However, physicians lack tools to distinguish early lesions that are aggressive from those that are indolent. To address this problem, we have brought together a multidisciplinary team composed of experts in urology, pathology, cancer genomics, proteomics, bioinformatics and biology. Together, we will characterize early prostate cancers and their precursor lesions for genomic and proteomic changes and use these data to construct evolutionary trees. From this we will identify clinically useful changes that could be used to distinguish indolent (“dead-end”) lesions from those that are potentially aggressive.

We will focus on 1) investigating the early genomic evolution of good and bad outcome prostate cancer in histologically defined prostate cancers and precursor lesions in fixed tissues; and 2) defining the genomic heterogeneity of good and bad outcome prostate cancer and the downstream consequences in transcript, protein and glycoprotein expression in frozen tissues. An integrated approach using fixed and frozen tissues will allow us to delineate the early genomic lesions in prostate cancer, define which are selected to evolve into more aggressive and which end up as non-aggressive (“dead-end”) lesions, and characterize the downstream effects of these selected changes in cellular transcription, protein expression, and protein glycosylation. 

A systematic study of the events in prostate cancer during its development and evolution will help address the issues of overtreatment by providing prognostic features and biomarkers that help select men for definitive treatment or observation.