Prostate Cancer Prognostics Based on Genome Architecture
Abstract
Prostate cancer is a leading cause of cancer in the United States. By current diagnosis methods, many men are receiving treatments for prostate cancers that if left untreated would not become life-threatening during the patient s life. These men have an unnecessary burden and reduction in the quality of their life from the side effects of receiving these needless treatments. The problem of overtreatment is caused by the fact that there is a lack of reliable prognostic markers to identify the prostate cancers that would remain asymptomatic from aggressive cancers. Currently, clinicians base decisions on whether or not to treat prostate cancer on serum prostate-specific antigen (PSA) levels, the size of the tumor, if the cancer has breached the prostate to spread beyond prostate tissue and changes in the shape of cells and the way cells are arranged in the patient s tissue sample. These criteria, however, are frequently subjective and do not accurately detect only the cancers that require treatment. Novel biomarkers of aggressive prostate cancer are greatly needed to predict the likely outcomes of the disease and help guide therapeutic decisions. We propose here to develop a novel strategy for the prognosis of prostate cancer, which in the long term will enable oncologists to determine which patients require immediate treatment and those for whom monitoring alone is the best option. This method is based on our ongoing studies of how genetic material is organized inside the cell. The vast majority of a cell s genes are found in its nucleus. Recent work, from our laboratory and many others, has demonstrated that each gene occupies a particular position within the nucleus. Importantly, it is now becoming clear that the spatial arrangement of genes changes inside the nucleus when cells become cancerous. In the work proposed here, we will take advantage of these changes in location, and we will identify genes that are in different positions in aggressive prostate cancer compared to non-aggressive cancer, benign and normal prostate tissues. We will use genes that change the location in aggressive cancers as a prognosis tool to detect cancers that require treatment. Our approach has a high probability of success since we have recently demonstrated its feasibility in detecting prostate and breast cancer in general. We will now adapt these studies to detect specifically aggressive prostate cancer. We will test the usefulness of the candidate genes we identify as prognostic markers by analysis of a large number of tumor samples. In particular, we will ask whether these genes are suitable to predict whether the tumor will recur, will metastasize, or be lethal. Successful completion of this study will ideally position us to develop a routine prognostic laboratory test by optimizing and standardizing every step of our method. Importantly, our approach is well suited for routine use and, if successful, may become available to clinicians within 5-7 years. Our approach requires only a very small tissue sample for analysis so it does not require additional invasive procedures for a patient. Moreover, it is relatively quick and inexpensive. The scientific technique our approach utilizes (fluorescence in situ hybridization) is already used in diagnostic labs; therefore, after thorough validation, our prognostic test could easily be integrated into clinical use. Moreover, it overcomes the limitations of the current diagnostic procedures as it produces measurable results and will be useful in reducing overtreatment by discriminating between aggressive and non-aggressive cancers. This approach can either be used as a stand-alone assay or in combination with standard pathology testing. This new method will benefit all biopsy patients and has the potential become a frontline clinical tool for prostate cancer to reduce overtreatment, but without increasing undertreatment. Most importantly, we hope to find markers that will ai
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510322
Entities
People
- Tom Misteli
Organizations
- National Cancer Institute
- United States Army