Precision Oncology-Based Therapeutic Targeting in Mesothelioma
Abstract
The proposed research project, Precision Oncology-Based Therapeutic Targeting in Mesothelioma will address the FY18 PRCRP Topic Area of mesothelioma. It will also address the FY18 PRCRP Military Relevance Focus Area of gaps in cancer prevention, screening, early detection, diagnosis, treatment, and/or survivorship that may affect the general population but have a particularly profound impact on the health and well-being of military Service members, Veterans, and their beneficiaries. Specifically, it will address a gap in treatment of patients with mesothelioma. In this project, our objective is to develop a precision oncology-based treatment strategy against mesothelioma. Mesothelioma is a devastating cancer in which the majority of patients will die from their cancer. There has not been a major new drug approved for treating mesothelioma by the Federal Drug Administration (FDA) in over 10 years. In the proposed study, we plan to use laboratory studies (including test tube experiments and mice studies) to evaluate new strategies for the treatment of mesothelioma. Most cases of mesothelioma have abnormalities in a pathway of the cell that controls the division of the cell, which is called the cell cycle. We have previously conducted studies on some anti-cancer drugs that target the cell cycle. Recently, three drugs that each target the cell cycle have been approved by the FDA for use in advanced breast cancer. Thus, there is a high likelihood that our approach will lead to an impact for patients. There is also evidence that other pathways within the mesothelioma cancer cell contribute to mesothelioma cancer growth. We would like to determine how to best target separate pathways in the cell (one being the cell cycle and the second being one of three separate, but related, pathways). To do so, we plan to use precision oncology to aid these efforts. Recently, the term precision oncology has become commonplace cancer research. In precision oncology, one uses laboratory tests from patients to pick the best treatments for a particular individual. Our hypothesis is that using a genomic test (call mRNA expression testing) to identify the best combinations of therapies to target the cell cycle and other cancer survival pathways will serve as an effective therapy against mesothelioma. Information gained from this study will help to aid in the future design of clinical trials in mesothelioma. If this project is successful, it could lead to a significant advance in the treatment of mesothelioma. At the end of the 2-year project, we will have enough preliminary data to design a clinical trial involving cell cycle inhibitors in combination with other cancer drugs already approved for other cancers. In addition, the additional data on reactive oxygen species will allow us to apply for additional national funding to design studies to move the combination of targeting the cell cycle and reactive oxygen species forward to the clinic. Relevance to mesothelioma to active duty Service members, Veterans, and other military beneficiaries. Mesothelioma is a devastating cancer that arises from the lining of the lungs or abdomen. In the United States, approximately 3,300 patients are diagnosed with mesothelioma every year, and about 3,000 patients die from mesothelioma every year. So, it is incurable in nearly all cases. The last FDA approval for chemotherapy for mesothelioma was in 2004 for the drug pemetrexed, but this drug only helps to extend the life of someone with advanced mesothelioma about 3 months. The chemical asbestos (produced as tiny fibers) has been used in the past for insulation, including in Navy ships. Asbestos exposure is recognized as a significant risk for development of mesothelioma. Many Veterans will have had exposure to asbestos in Navy ships or shipbuilding. Chemicals called carbon nanotubes are also a possible risk factor for mesothelioma, and these are going into products such as Kevlar vests. Mining is also a re
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910612
Entities
People
- Mark Klein
Organizations
- Minneapolis VA Medical Center
- United States Army