Proteomic-Based Biomarkers for Risk of Progression in Early Prostate Cancer
Abstract
Prostate cancer is the second leading cause of cancer-related death in men; however, most men who are diagnosed with prostate cancer will not die of the disease. Therefore, the most important question facing prostate cancer researchers and clinicians is discovering ways to better determine which men have aggressive prostate cancer and are at risk of dying. This is especially important since prostate cancer treatment can cause long-term health changes, such as sexual and urinary difficulties. “Active surveillance” is an increasingly common way of managing prostate cancer, where men with prostate cancer who have less aggressive disease receive no immediate treatment, but instead are watched closely to make sure the disease does not worsen before treatment can provide a cure. Usually, clinicians use factors such as laboratory tests and biopsies to determine who has aggressive prostate cancer; however, these tools are invasive and their predictive accuracy is not perfect. Researchers have developed other genetic-based tools to look for aggressive cancer, though many of these require patient tissue (that is, they are invasive) and have not been shown to help men on surveillance. Finding markers of prostate cancer aggression that can be obtained with blood draws would greatly help disease management. Our group previously looked at a protein that can be found in the blood, caveolin-1, and discovered that it may help determine which patients have aggressive disease. Using data obtained through mass spectrometry (a technique to measure protein levels) in the blood of men with aggressive disease and of men with slow-growing cancer, I determined that levels of seven proteins, VTN, GELS, APOA, APOB, APOE, FBLN3, and VTDB, may help determine who has aggressive disease. My hypothesis is that, by confirming the differences in levels of these proteins between men with aggressive disease and those with less aggressive disease, then looking further at these protein levels in men on active surveillance, I can see which men have cancer that can worsen and place them at risk of dying. I propose to first use antibodies (which bind proteins) and a detection system called ELISA to confirm that the level of each of the seven blood proteins detected in the mass spectrometry data is truly different in the original two groups of men with aggressive disease or slow-growing disease. The proteins that are confirmed to be expressed differently in the two groups will then be measured in a larger group of men on active surveillance to compare the men whose disease got worse while they were being watched to those whose disease did not get worse in order to see whether the protein levels were different in those whose disease worsened. This study will advance the treatment of localized prostate cancer by more correctly determining who has aggressive disease when the cancer is first diagnosed, thereby helping men and their doctors decide who should be on surveillance. The study focuses on developing personalized treatment and surveillance strategies and will use large databases and analyses to help achieve these goals. I am a urologic oncology clinical fellow who is currently gaining the additional skills needed to pursue my career goals of both treating patients with prostate cancer and researching ways to better determine who needs treatment. While I have extensive clinical training and have completed a number of prior research projects, this study award will give me the skills needed to look for markers of prostate cancer aggression and use statistics to determine whether they are useful for men with prostate cancer. My mentor, Dr. Thompson, is an accomplished prostate cancer researcher who has years of experience investigating prostate cancer aggression. Dr. Kim, my co-mentor, is an oncologist who treats men with prostate cancer and also is in charge of a research study of men on active surveillance to improve its outcomes and safety.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810173
Entities
People
- Justin R Gregg
Organizations
- United States Army
- University of Texas at Austin