Using Metabolic Pathways to Improve Diagnosis and Risk Stratification of Prostate Cancer
Abstract
Prostate cancer (PCa) is the second leading cause of cancer death in men; however, most men with PCa will ultimately die of other causes. This has led to the issue that since the treatment for PCa carries significant complication risks with it as well, the risks of over-treating men who would have died of other causes had they not been treated has to be weighed against the risks of undertreating those men who are risk of death from prostate cancer. Until recently, the most reliable methods to differentiate such men with low-risk versus high-risk disease was with the use of a physical exam, the blood test PSA (prostate-specific antigen), and biopsy results from the prostate. Such information was of benefit, but still led to many men in whom the benefit from treatment remains uncertain. Recent advances in the diagnosis and risk stratification of prostate cancer have incorporated the use of magnetic resonance imaging. Use of imaging characteristics has significantly improved our ability to diagnose men with high-risk disease, while also decrease the rate at which men with low-risk disease are even diagnosed anymore. However, the advancement has only been modest and there remains a great deal of progress to be made. An emerging area of research is the study of cancer metabolism. It is believed by many that a better understanding of how cancer cells metabolize nutrients to survive will improve our ability to differentiate aggressive tumors from indolent ones. Tumor cells utilize energy sources such as sugars, fats, and protein (glucose, fatty acids, and amino acids) to generate energy and cellular building blocks for growth. It turns out that the way tumors utilize these energy sources is different than the way normal cells use these energy sources. The premise behind this study is to study how prostate cancer uses a specific energy source, pyruvate, and to understand how this utilization varies between benign tissues and indolent tumors versus aggressive tumors. It is our hypothesis that by understanding how tumors use pyruvate, specifically a particular nuclear labeled pyruvate with a heavy carbon atom on carbon two, [2-13C]pyruvate, we will better be able to differentiate aggressive from indolent prostate cancer. To perform these studies in the first aim of this study, prostate cells will be studied in the cell culture setting to examine how cells of varying aggressiveness metabolize [2-13C]pyruvate. Furthermore, specialized instruments will measure how the cells produce waste products of metabolism (lactic acid) as well as take in oxygen to maintain their metabolism. With this understanding, Aim 2 will be to translate these findings into studying tumors as they grow in mice. These experiments will allow us to test the knowledge gained from Aim 1 in an animal model setting to see if the observed differences in tumor metabolism do indeed differentiate high-grade from low-grade tumors. The ultimate expected impact of this work is that it will lay the groundwork for human translational studies. Our institution is well positioned for translating this novel approach of metabolic MRI to humans as we are already in possession of the highly specialized equipment necessary to accomplish this goal. The preclinical data generated from these studies will help us design human studies to further understand if metabolic imaging can indeed improve our ability to differentiate men with aggressive versus indolent prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610414
Entities
People
- Mohummad Siddiqui
Organizations
- United States Army
- University of Maryland, Baltimore