Transfer RNA-Derived Fragments as Novel Diagnostic and Functional Targets for Malignant Mesothelioma
Abstract
Malignant mesothelioma poses a significant health issue to members of the military, with Service members exposed to high levels of asbestos. It is a designated priority area outlined in the Fiscal Year 2019 (FY19) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas to be studied. Mesothelioma is an aggressive tumor of the lining of the lungs primarily caused by inhalation of asbestos fibers. It has a poor prognosis and there is no effective treatment, with an average survival time of less than 12 months after first diagnosis. This project explores the potential for small fragments of genetic material called transfer RNA-derived fragments (TRFs) as novel diagnostic, early disease, and disease progression biomarkers as well as targets for therapy in mesothelioma. Currently, diagnosis of mesothelioma is difficult and may take up to 3 months. In addition, most mesothelioma diagnosis is performed using tissue biopsy, but sampling error is common given the large area of the lung surface. Patients are often subjected to invasive procedures to obtain many large biopsies from multiple sites in order to secure a diagnosis. The costs, delay, and adverse events associated with this approach are well recognized. By investigating these molecules in blood from patients, we hope to determine if these markers distinguish mesothelioma from normal individuals and patients with other cancers and lung diseases. The data generated in this study may identify tRFs that are expressed early in the development of mesothelioma and hence, be used for screening high-risk populations using a simple and inexpensive blood test. Early diagnosis of mesothelioma is imperative if we are ever going to witness significant improvements in survival amongst patients with this disease. Current therapies are fundamentally ineffective, and this can in part be attributed to the advanced stage of disease at diagnosis. This study will also determine the role these tRFs play in the body and more specifically in mesothelioma cells, which will help identify new therapeutic approaches for this disease. Clearly, this study has short- and long-term goals. In the short term we will be able to determine if tRFs that we recently discovered in serum from mesothelioma patients are significantly different from healthy people as well as those with other cancers and different lung diseases. This would reduce the need for invasive biopsies and speed up the diagnostic process, reducing the stress to patients waiting for a diagnosis and allowing faster treatment. In the medium term, identifying tRFs early in the disease process would allow screening of high-risk populations and ultimately, earlier treatment, which would impact patient survival and have a major impact on reducing health care costs. Clearly, these two aims are going to be the easiest to translate from research into practice. In the long term, understanding the role of TRFs in mesothelioma development and growth may allow us to develop better treatments to improve patient survival. Many high-risk individuals such as those in the armed forces or military Veterans experience extreme anxiety and depression, with fear they will develop cancer. An early detection test for mesothelioma will help alleviate much of that anxiety for individuals exposed to asbestos. For those that test positive, it will allow early disease intervention which, given the rapid developments in the field, is more likely to have a successful outcome.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010516
Entities
People
- Steven Mutsaers
Organizations
- United States Army
- University of Western Australia