One of the main challenges for medicine in the early part of 21st century is to incorporate knowledge of thehuman genome into the medical management of patients, thereby yielding more precise diagnoses andmechanism-based deployment of therapy. Nowhere is this need more pressing than in the treatment of menwith prostate cancer. Prostate cancer is a major cause of death and morbidity, yet large numbers of men arebelieved to harbor tumors that are indolent even in the absence of therapy. As such, many men receiveunnecessary treatment with its attendant effects, and others die of disease despite aggressive therapy. Wehypothesize that the variability in the natural history of CaP is determined by heretofore unrecognizedmolecular heterogeneity of the disease. We therefore propose here to identify a gene expression signaturethat distinguishes indolent from lethal disease.This Project has 3 Specific Aims:
Aim 1 : Collect, register, and process archival formalin-fixed paraffin embedded (FFPE) samples from theSwedish Watchful Waiting (WW) cohorts with up to 30 years clinical follow up.
Aim 2 : Develop molecular signatures of lethal and indolent prostate cancer on the Watchful Waiting FFPEsamples using an Illumina expression array platform with over 6000 genes developed specifically formolecular signature discovery.
Aim 3 : Validate the signatures on Swedish WW cases not used in Aim 2 and test for the presence of theseprofiles in tumor samples (n=100) from the Physicians' Health Study (PHS).At the conclusion of this proposal, we expect to have discovered and validated molecular predictors ofprostate cancer outcome that are appropriate for further clinical development. To accomplish these goals, wehave assembled a multidisciplinary team of investigators with a long track record of collaboration, and withparticular expertise in the clinical, pathological and epidemiological aspects of prostate cancer, in thedevelopment and deployment of genomics technologies, and in advanced computational and statisticalanalysis.
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